Trial Outcomes & Findings for BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours (NCT NCT01169675)

NCT ID: NCT01169675

Last Updated: 2014-06-09

Results Overview

Occurence of DLT during the first course of treatment to determine the maximum tolerated dose (MTD) of Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 53 participants
• Primary outcome timeframe: DLT were assessed during the first cycle (days 1-21)
• Results posted on: 2014-06-09

Participant Flow

Participant milestones

Measure	Continuous Afatinib 30 mg Continuous Afatinib 30 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Continuous Afatinib 40 mg Continuous Afatinib 40 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Pulsed Afatinib 50 mg Pulsed Afatinib 50 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Pulsed Afatinib 60 mg Pulsed Afatinib 60 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Pulsed Afatinib 70 mg Pulsed Afatinib 70 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.
Overall Study STARTED	20	3	7	17	6
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	20	3	7	17	6

Reasons for withdrawal

Measure	Continuous Afatinib 30 mg Continuous Afatinib 30 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Continuous Afatinib 40 mg Continuous Afatinib 40 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Pulsed Afatinib 50 mg Pulsed Afatinib 50 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Pulsed Afatinib 60 mg Pulsed Afatinib 60 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.	Pulsed Afatinib 70 mg Pulsed Afatinib 70 mg plus Pemetrexed. Afatinib is the same intervention as BIBW 2992.
Overall Study Progressive disease	13	2	5	15	1
Overall Study Dose Limiting Toxicity (DLT)	1	0	0	0	2
Overall Study Adverse Event	5	1	2	0	0
Overall Study Withdrawal by Subject	1	0	0	1	2
Overall Study Other Reason Not Defined Above	0	0	0	1	1

Baseline Characteristics

BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours

Baseline characteristics by cohort

Measure	Continuous Afatinib 30 mg n=20 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 Participants Pulsed Afatinib 70 mg plus Pemetrexed	Total n=53 Participants Total of all reporting groups
Age, Continuous	60.2 years STANDARD_DEVIATION 9.4 • n=5 Participants	53.7 years STANDARD_DEVIATION 16.6 • n=7 Participants	69.6 years STANDARD_DEVIATION 10.5 • n=5 Participants	57.9 years STANDARD_DEVIATION 10.7 • n=4 Participants	64.8 years STANDARD_DEVIATION 7.4 • n=21 Participants	60.8 years STANDARD_DEVIATION 10.7 • n=8 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants	2 Participants n=21 Participants	27 Participants n=8 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	26 Participants n=8 Participants

PRIMARY outcome

Timeframe: DLT were assessed during the first cycle (days 1-21)

Population: Treated Set includes all patients that received treatment of Afatinib or Pemetrexed that who were evaluable for MTD determination

Occurence of DLT during the first course of treatment to determine the maximum tolerated dose (MTD) of Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).

Outcome measures

Measure	Continuous Afatinib 30 mg n=19 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=6 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 Participants Pulsed Afatinib 70 mg plus Pemetrexed
Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set	6 participants	2 participants	1 participants	6 participants	4 participants

SECONDARY outcome

Timeframe: DLT were assessed during all cycles of treatment

Population: Treated Set includes all patients that received treatment of Afatinib or Pemetrexed

Occurence of DLT during all courses of treatment with Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).

Outcome measures

Measure	Continuous Afatinib 30 mg n=20 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 Participants Pulsed Afatinib 70 mg plus Pemetrexed
Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set	11 participants	2 participants	3 participants	11 participants	4 participants

SECONDARY outcome

Timeframe: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

Population: Treated Set includes all patients that received treatment of Afatinib or Pemetrexed

Objective Response is defined as complete response or partial response according to the response evaluation criteria in solid tumours (RECIST) version 1.1.

Complete Response (CR): disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR): at least 30% decrease of the sum of longest diameter (LD) of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions together with an absolute increase in the sum of LD of at least 5 millimeters; Stable Disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD.

Outcome measures

Measure	Continuous Afatinib 30 mg n=20 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 Participants Pulsed Afatinib 70 mg plus Pemetrexed
Objective Response (OR)	2 participants	0 participants	0 participants	2 participants	0 participants

SECONDARY outcome

Timeframe: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

Population: Treated Set includes all patients that received treatment of Afatinib or Pemetrexed

Disease Control is defined as complete response, partial response, or stable disease according to the response evaluation criteria in solid tumours (RECIST) version 1.1.

Outcome measures

Measure	Continuous Afatinib 30 mg n=20 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 Participants Pulsed Afatinib 70 mg plus Pemetrexed
Disease Control	6 participants	1 participants	3 participants	6 participants	2 participants

SECONDARY outcome

Timeframe: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

Population: Treated Set includes all patients that received treatment of Afatinib or Pemetrexed

PFS was defined as the time from the first treatment to the occurence of tumour progression or death, whichever came first. It was assessed according to RECIST version 1.1 criteria.

Outcome measures

Measure	Continuous Afatinib 30 mg n=20 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 Participants Pulsed Afatinib 70 mg plus Pemetrexed
Progression Free Survival (PFS)	2.49 months Interval 1.21 to 3.97	2.52 months Interval 1.14 to 5.32	2.56 months Interval 1.21 to 6.5	2.52 months Interval 1.21 to 4.13	2.69 months Interval 0.82 to 7.85

SECONDARY outcome

Timeframe: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

Population: Treated Set: all patients that received treatment of Afatinib or Pemetrexed and who were evaluated for the longest diameter of the target lesions.

Tumour shrinkage is defined as the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions.

Outcome measures

Measure	Continuous Afatinib 30 mg n=17 Participants Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=2 Participants Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 Participants Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=16 Participants Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=3 Participants Pulsed Afatinib 70 mg plus Pemetrexed
Tumour Shrinkage Patients with any decrease in tumour size	10 participants	2 participants	3 participants	5 participants	1 participants
Tumour Shrinkage Patients having >30% decrease in tumour size	2 participants	0 participants	0 participants	2 participants	0 participants

Adverse Events

Continuous Afatinib 30 mg

Serious events: 9 serious events

Other events: 20 other events

Deaths: 0 deaths

Continuous Afatinib 40 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Pulsed Afatinib 50 mg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Pulsed Afatinib 60 mg

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Pulsed Afatinib 70 mg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Continuous Afatinib 30 mg n=20 participants at risk Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 participants at risk Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 participants at risk Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 participants at risk Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 participants at risk Pulsed Afatinib 70 mg plus Pemetrexed
Gastrointestinal disorders Intestinal obstruction	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Intestinal prolapse	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Dysphagia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Gastritis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Vomiting	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Death	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Fatigue	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Lower respiratory tract infection	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Pneumonia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Sepsis	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Urinary tract infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Neck pain	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Altered state of consciousness	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Confusional state	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Renal failure	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.

Other adverse events

Measure	Continuous Afatinib 30 mg n=20 participants at risk Continuous Afatinib 30 mg plus Pemetrexed	Continuous Afatinib 40 mg n=3 participants at risk Continuous Afatinib 40 mg plus Pemetrexed	Pulsed Afatinib 50 mg n=7 participants at risk Pulsed Afatinib 50 mg plus Pemetrexed	Pulsed Afatinib 60 mg n=17 participants at risk Pulsed Afatinib 60 mg plus Pemetrexed	Pulsed Afatinib 70 mg n=6 participants at risk Pulsed Afatinib 70 mg plus Pemetrexed
Eye disorders Eye discharge	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Eye irritation	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Eye oedema	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Foreign body sensation in eyes	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Lacrimation increased	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Anaemia	50.0% 10/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	71.4% 5/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	58.8% 10/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Leukopenia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Neutropenia	30.0% 6/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Blood and lymphatic system disorders Thrombocytopenia	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Cardiac disorders Bradycardia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Ear and labyrinth disorders Ear discomfort	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Cataract	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Dry eye	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Ocular hyperaemia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Photopsia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Vision blurred	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Eye disorders Visual impairment	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Abdominal distension	25.0% 5/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Abdominal pain	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Abdominal pain upper	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Anorectal discomfort	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Aptyalism	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Constipation	35.0% 7/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	71.4% 5/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Diarrhoea	95.0% 19/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 3/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	71.4% 5/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	82.4% 14/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 6/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Dry mouth	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Dyspepsia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Dysphagia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Flatulence	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Gingival pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Glossodynia	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Haemorrhoidal haemorrhage	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Haemorrhoids	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Intestinal prolapse	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Lip swelling	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Lip ulceration	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Nausea	65.0% 13/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	66.7% 2/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	57.1% 4/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	76.5% 13/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	83.3% 5/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Oesophagitis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Proctalgia	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Rectal haemorrhage	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Salivary hypersecretion	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Stomatitis	75.0% 15/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 3/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	85.7% 6/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	64.7% 11/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	83.3% 5/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Gastrointestinal disorders Vomiting	45.0% 9/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	71.4% 5/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	64.7% 11/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Chest discomfort	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Chest pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Chills	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Face oedema	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Fatigue	90.0% 18/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	66.7% 2/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 7/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	94.1% 16/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	83.3% 5/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Feeling cold	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Gait disturbance	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Influenza like illness	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Local swelling	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Mass	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Oedema	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Oedema peripheral	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	42.9% 3/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Pain	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Pyrexia	25.0% 5/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	57.1% 4/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Thirst	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
General disorders Unevaluable event	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Hepatobiliary disorders Hepatic pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Hepatobiliary disorders Hyperbilirubinaemia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Immune system disorders Hypersensitivity	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Acute sinusitis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Candidiasis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Catheter site infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Cystitis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Fungal infection	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Kidney infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Localised infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Lower respiratory tract infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Nasopharyngitis	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Omphalitis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Oral candidiasis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Oral herpes	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Paronychia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Pneumonia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Respiratory tract infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Rhinitis	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Sinusitis	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Tinea infection	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Infections and infestations Urinary tract infection	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Injury, poisoning and procedural complications Contusion	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Alanine aminotransferase increased	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	35.3% 6/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Aspartate aminotransferase increased	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Blood alkaline phosphatase increased	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	29.4% 5/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Blood bilirubin increased	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Blood creatinine increased	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Blood lactate dehydrogenase increased	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Ejection fraction decreased	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Gamma-glutamyltransferase increased	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Haemoglobin decreased	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Neutrophil count decreased	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Platelet count decreased	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Platelet count increased	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Investigations Weight decreased	45.0% 9/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	57.1% 4/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	29.4% 5/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Decreased appetite	80.0% 16/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 3/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	71.4% 5/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	76.5% 13/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 6/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Dehydration	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypocalcaemia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypokalaemia	25.0% 5/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	41.2% 7/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypomagnesaemia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Arthralgia	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Back pain	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	42.9% 3/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	29.4% 5/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Groin pain	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Muscle spasms	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Muscle tightness	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Muscular weakness	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	42.9% 3/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	66.7% 2/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Aphonia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Balance disorder	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Dizziness	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 3/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Dysgeusia	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 2/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Headache	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Lethargy	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Memory impairment	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Neuropathy peripheral	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Paraesthesia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Restless legs syndrome	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Somnolence	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Nervous system disorders Tremor	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Abnormal dreams	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Anxiety	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Confusional state	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Depression	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Insomnia	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Psychiatric disorders Panic attack	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Bladder pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Bladder spasm	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Chromaturia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Dysuria	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Haematuria	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Pollakiuria	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Renal and urinary disorders Urinary retention	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Reproductive system and breast disorders Penile discharge	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Reproductive system and breast disorders Penile oedema	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Reproductive system and breast disorders Penile pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Reproductive system and breast disorders Scrotal oedema	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Reproductive system and breast disorders Vulvovaginal pruritus	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	29.4% 5/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	66.7% 2/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	42.9% 3/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	45.0% 9/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	66.7% 2/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	28.6% 2/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	29.4% 5/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	50.0% 3/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Nasal dryness	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	66.7% 2/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Acne	20.0% 4/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Alopecia	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Dermatitis acneiform	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Dry skin	30.0% 6/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	42.9% 3/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Erythema	25.0% 5/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Hangnail	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Nail discolouration	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Night sweats	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Pain of skin	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	11.8% 2/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	30.0% 6/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	42.9% 3/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	23.5% 4/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Petechiae	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Pruritus	25.0% 5/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	57.1% 4/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Rash	65.0% 13/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	100.0% 3/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	71.4% 5/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	88.2% 15/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	83.3% 5/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Rash macular	5.0% 1/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Skin discolouration	10.0% 2/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	16.7% 1/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Vascular disorders Flushing	15.0% 3/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	33.3% 1/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	17.6% 3/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Vascular disorders Hypotension	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	14.3% 1/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.
Vascular disorders Peripheral coldness	0.00% 0/20 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/3 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/7 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	5.9% 1/17 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.	0.00% 0/6 • Starting with first administration of trial drug (Afatinib or Pemetrexed) and ending 28 days after the last administration of trial drug.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER