Trial Outcomes & Findings for A Study for Non-Smoker Patients With Nonsquamous Non-Small Cell Lung Cancer (NCT NCT00550173)

NCT ID: NCT00550173

Last Updated: 2013-02-13

Results Overview

PFS is defined as the time from randomization to the first date of progressive disease (PD; either objectively determined or clinical progression) or death from any cause. PD was defined as at least a 20% increase in sum of longest diameter of target lesions as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. Time to disease progression was censored at the date of death.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 247 participants
• Primary outcome timeframe: Randomization to measured PD up to 38 months
• Results posted on: 2013-02-13

Participant Flow

Participant milestones

Measure	Pemetrexed + Erlotinib Pemetrexed 500 milligrams per meter squared (mg/m\^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed Pemetrexed 500 mg/m\^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Overall Study STARTED	81	82	84
Overall Study Qualified Participants	78	82	80
Overall Study Not Discontinued at 18 Months	9	19	11
Overall Study COMPLETED	9	19	11
Overall Study NOT COMPLETED	72	63	73

Reasons for withdrawal

Measure	Pemetrexed + Erlotinib Pemetrexed 500 milligrams per meter squared (mg/m\^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed Pemetrexed 500 mg/m\^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Overall Study Death	45	38	50
Overall Study Physician Decision	1	2	2
Overall Study Withdrawal by Subject	9	12	17
Overall Study Sponsor Decision	13	7	1
Overall Study Lost to Follow-up	4	4	3

Baseline Characteristics

A Study for Non-Smoker Patients With Nonsquamous Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Pemetrexed + Erlotinib n=78 Participants Pemetrexed 500 mg/m\^2 of body surface area, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=82 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.	Total n=240 Participants Total of all reporting groups
Age Continuous	56.0 years STANDARD_DEVIATION 11.72 • n=5 Participants	53.9 years STANDARD_DEVIATION 10.49 • n=7 Participants	56.1 years STANDARD_DEVIATION 13.04 • n=5 Participants	55.3 years STANDARD_DEVIATION 11.78 • n=4 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	54 Participants n=7 Participants	45 Participants n=5 Participants	157 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	28 Participants n=7 Participants	35 Participants n=5 Participants	83 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	18 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants	35 participants n=4 Participants
Race/Ethnicity, Customized African	2 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized East Asian (enrolled in an East Asian country)	41 participants n=5 Participants	49 participants n=7 Participants	43 participants n=5 Participants	133 participants n=4 Participants
Race/Ethnicity, Customized East Asian (enrolled in non-East Asian Country)	4 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants
Race/Ethnicity, Customized West Asian	13 participants n=5 Participants	25 participants n=7 Participants	24 participants n=5 Participants	62 participants n=4 Participants
Region of Enrollment Australia	3 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Brazil	15 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants	28 participants n=4 Participants
Region of Enrollment China	14 participants n=5 Participants	17 participants n=7 Participants	15 participants n=5 Participants	46 participants n=4 Participants
Region of Enrollment Hong Kong	0 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment India	15 participants n=5 Participants	27 participants n=7 Participants	25 participants n=5 Participants	67 participants n=4 Participants
Region of Enrollment Korea, Republic of	20 participants n=5 Participants	20 participants n=7 Participants	13 participants n=5 Participants	53 participants n=4 Participants
Region of Enrollment Taiwan	7 participants n=5 Participants	9 participants n=7 Participants	13 participants n=5 Participants	29 participants n=4 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	9 participants n=4 Participants
Height at Baseline	159.3 centimeter (cm) STANDARD_DEVIATION 8.70 • n=5 Participants	160.3 centimeter (cm) STANDARD_DEVIATION 8.38 • n=7 Participants	160.1 centimeter (cm) STANDARD_DEVIATION 8.84 • n=5 Participants	159.9 centimeter (cm) STANDARD_DEVIATION 8.61 • n=4 Participants
Weight at Baseline	59.6 kilogram (kg) STANDARD_DEVIATION 11.76 • n=5 Participants	59.9 kilogram (kg) STANDARD_DEVIATION 12.17 • n=7 Participants	58.9 kilogram (kg) STANDARD_DEVIATION 10.82 • n=5 Participants	59.5 kilogram (kg) STANDARD_DEVIATION 11.56 • n=4 Participants
Body Mass Index (BMI)	23.5 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 4.54 • n=5 Participants	23.3 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 3.87 • n=7 Participants	23.0 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 3.87 • n=5 Participants	23.2 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 4.09 • n=4 Participants
Body Surface Area (BSA)	1.6 meter squared (m^2) STANDARD_DEVIATION 0.17 • n=5 Participants	1.6 meter squared (m^2) STANDARD_DEVIATION 0.18 • n=7 Participants	1.6 meter squared (m^2) STANDARD_DEVIATION 0.17 • n=5 Participants	1.6 meter squared (m^2) STANDARD_DEVIATION 0.17 • n=4 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0	10 participant n=5 Participants	20 participant n=7 Participants	16 participant n=5 Participants	46 participant n=4 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1	61 participant n=5 Participants	56 participant n=7 Participants	60 participant n=5 Participants	177 participant n=4 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2	6 participant n=5 Participants	6 participant n=7 Participants	4 participant n=5 Participants	16 participant n=4 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 3	1 participant n=5 Participants	0 participant n=7 Participants	0 participant n=5 Participants	1 participant n=4 Participants
Histological Subtype Adenocarcinoma (adeno)	72 participants n=5 Participants	76 participants n=7 Participants	77 participants n=5 Participants	225 participants n=4 Participants
Histological Subtype Non-adenocarcinoma (non-adeno)	6 participants n=5 Participants	6 participants n=7 Participants	3 participants n=5 Participants	15 participants n=4 Participants

PRIMARY outcome

Timeframe: Randomization to measured PD up to 38 months

Population: Qualified Intent to Treat (Q-ITT) Population defined as all participants with nonsquamous histology, who were randomized to therapy.

PFS is defined as the time from randomization to the first date of progressive disease (PD; either objectively determined or clinical progression) or death from any cause. PD was defined as at least a 20% increase in sum of longest diameter of target lesions as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. Time to disease progression was censored at the date of death.

Outcome measures

Measure	Pemetrexed + Erlotinib n=78 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=82 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Progression-Free Survival (PFS)	7.4 months Interval 4.4 to 12.9	3.8 months Interval 2.7 to 6.3	4.4 months Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: Randomization to measured disease progression up to 38 months

Population: Q-ITT Population - Tumor Analyzable (Q-ITT-TA) Population: defined as all participants with nonsquamous histology, who were randomized to therapy and had measurable or evaluable lesions at baseline.

TRR was defined as the number of responders (complete or partial) divided by the number of participants qualified for tumor response, as assessed using the RECIST version 1.0 guideline, multiplied by 100. RECIST guidelines: CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Measure	Pemetrexed + Erlotinib n=76 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=82 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Percentage of Participants With a Tumor Response of Complete Response (CR) or Partial Response (PR) [Tumor Response Rate (TRR)]	44.7 percentage of participants	29.3 percentage of participants	10.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to date of death from any cause up to 45.5 months

Population: Q-ITT Population: defined as all participants with nonsquamous histology, who were randomized to therapy. Survival time was censored at the date of last contact for participants who were still alive or lost to follow-up, number of participants censored 35 (pemetrexed plus erlotinib), 44 (erlotinib) and 31 (pemetrexed).

OS is defined as the time from randomization to the date of death from any cause.

Outcome measures

Measure	Pemetrexed + Erlotinib n=78 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=82 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Overall Survival (OS)	20.5 months Interval 17.1 to 25.0	22.8 months Interval 18.2 to 29.5	17.7 months Interval 11.8 to 25.3

SECONDARY outcome

Timeframe: Randomization up to 39 months

Population: Safety Population defined as non-squamous participants who received at least 1 dose of study therapy (pemetrexed plus erlotinib or pemetrexed or erlotinib). One participant was assigned to pemetrexed (single therapy) but received erlotinib (single therapy) at first cycle and this lead to the discrepancy of participants for the safety analysis.

A summary of serious and all other non-serious adverse events (AEs), which include AEs reported for pharmacological toxicity, is located in the Reported Adverse Event module.

Outcome measures

Measure	Pemetrexed + Erlotinib n=78 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=83 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Number of Participants With Adverse Events Serious Adverse Events	25 participants	18 participants	22 participants
Number of Participants With Adverse Events Other Non-Serious Adverse Events	72 participants	76 participants	67 participants

SECONDARY outcome

Timeframe: Randomization to disease progression up to 38 months

Population: Q-ITT-TA Population: defined as all participants, with nonsquamous histology, who were randomized to therapy and had measurable or evaluable lesions at baseline.

DCR was defined as the percentage of participants with CR, PR, or SD divided by the number of randomized and treated participants as assessed using the RECIST criteria. CR was defined as the disappearance of all target lesions; PR was defined as 1) at least a 30% decrease in sum of longest diameter of target lesions or 2) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions; PD was defined as at least a 20% increase in sum of longest diameter of target lesions; SD was defined as small changes that did not meet the above criteria.

Outcome measures

Measure	Pemetrexed + Erlotinib n=76 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=82 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Percentage of Participants With CR, PR, and Stable Disease (SD) - Disease Control Rate (DCR)	64.5 percentage of participants	52.4 percentage of participants	56.3 percentage of participants

SECONDARY outcome

Timeframe: Randomization to first date of worsening of any of 6 LCSS symptom specific items or up to 12.4 months

Population: A subset of the Q-ITT Population that included participants with LCSS results; Q-ITT Population: defined as all participants, with nonsquamous histology, who were randomized to therapy.

TWS assessed using the LCSS a participant rated lung cancer instrument which consisted of 9 disease related symptoms and quality of life (QoL) items, with 6 subscales related to major lung cancer symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 summation items related to QoL (activity status, symptomatic distress, and overall QoL). Each item is marked on a visual analog scale (VAS) 0 (low symptoms/QoL items) to 100 (high symptoms/QoL items). The mean of the 6 subscales is used to calculate the average symptom burden index. TWS was measured from the date of study enrollment to the first date of a worsening in any 1 of the 6 LCSS symptom-specific items (as defined by a VAS 15-mm increase from baseline in the patient-reported score for any of these 6 items).

Outcome measures

Measure	Pemetrexed + Erlotinib n=70 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=71 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=65 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Time to Worsening of Symptoms (TWS) on Lung Cancer Symptoms Scale (LCSS)	1.0 months Interval 0.9 to 1.6	0.8 months Interval 0.8 to 1.2	1.5 months Interval 1.0 to 2.1

SECONDARY outcome

Timeframe: Randomization to date of PD or death up to 38 months

Population: A subset of the Q-ITT Population who had EGFR samples; Q-ITT Population: defined as all participants with nonsquamous histology, who were randomized to therapy.

EGFR mutation status was defined as: participants with any mutations detected were categorized as mutated and participants without any mutations detected were categorized as non-mutated.

Outcome measures

Measure	Pemetrexed + Erlotinib n=22 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=16 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=15 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Number of Participants With Mutated or Non-Mutated Epidermal Growth Factor Receptor (EGFR) Genotype Status Mutated	7 participants Interval 7.1 to	8 participants	9 participants
Number of Participants With Mutated or Non-Mutated Epidermal Growth Factor Receptor (EGFR) Genotype Status Non-mutated	10 participants	6 participants	3 participants
Number of Participants With Mutated or Non-Mutated Epidermal Growth Factor Receptor (EGFR) Genotype Status Mutation status unknown (treated as missing)	5 participants	2 participants	3 participants

SECONDARY outcome

Timeframe: Month 12

Population: Q-ITT Population: defined as all participants with nonsquamous histology, who were randomized to therapy.

OS time is censored at the date of last contact for participants who were still alive or lost to follow-up.

Outcome measures

Measure	Pemetrexed + Erlotinib n=78 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Erlotinib n=82 Participants Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Pemetrexed n=80 Participants Pemetrexed 500 mg/m\^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
Probability of OS at 12 Months	40.2 percent chance of survival Interval 28.3 to 51.8	26.2 percent chance of survival Interval 17.2 to 36.1	18.1 percent chance of survival Interval 9.1 to 29.4

Adverse Events

Pemetrexed + Erlotinib

Serious events: 25 serious events

Other events: 72 other events

Deaths: 0 deaths

Erlotinib

Serious events: 18 serious events

Other events: 76 other events

Deaths: 0 deaths

Pemetrexed

Serious events: 22 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pemetrexed + Erlotinib n=78 participants at risk Participants received pemetrexed 500 milligrams per meter squared (mg/m\^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21 day cycle until disease progression or unacceptable toxicity developed up to 39 months.	Erlotinib n=83 participants at risk Participants received erlotinib 150 mg, administered orally once daily in each 21 day cycle until disease progression or unacceptable toxicity developed up to 39 months.	Pemetrexed n=80 participants at risk Participants received pemetrexed 500 mg/m\^2 of body surface area, administered by intravenous (IV) infusion on Day 1 of each 21 day cycle until progression or unacceptable toxicity developed up to 39 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Febrile neutropenia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Leukopenia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Lymphopenia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Neutropenia	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Cardiac disorders Arrhythmia	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Cardiac disorders Cardio-respiratory arrest	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Cardiac disorders Myocardial infarction	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Cardiac disorders Pericardial effusion	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Ear and labyrinth disorders Vertigo positional	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Abdominal pain	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Abdominal pain upper	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Constipation	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Diarrhoea	5.1% 4/78 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Dyspepsia	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Gastric haemorrhage	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Gastric ulcer	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Gastritis	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Intestinal obstruction	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Nausea	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Stomatitis	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Vomiting	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Asthenia	2.6% 2/78 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Death	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Irritability	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Mucosal inflammation	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Pyrexia	3.8% 3/78 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Sudden death	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Hepatobiliary disorders Hepatitis acute	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Abscess	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Bronchitis	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Device related infection	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Herpes zoster	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Lower respiratory tract infection	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Pneumonia	2.6% 2/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Pneumonia bacterial	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Respiratory tract infection	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Respiratory tract infection bacterial	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Sepsis	2.6% 2/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Subcutaneous abscess	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Urinary tract infection	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Injury, poisoning and procedural complications Thoracic vertebral fracture	1.3% 1/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Haemoglobin decreased	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations White blood cell count decreased	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Decreased appetite	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Dehydration	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Hypocalcaemia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Hypokalaemia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Hypomagnesaemia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Hyponatraemia	2.6% 2/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	5.0% 4/80 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Bone pain	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Myalgia	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Dizziness	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Hemiplegia	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Nervous system disorder	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Neurotoxicity	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Radicular pain	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Renal and urinary disorders Renal failure chronic	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 2/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.2% 6/83 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 2/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Rash	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Vascular disorders Hypertension	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Vascular disorders Hypotension	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.

Other adverse events

Measure	Pemetrexed + Erlotinib n=78 participants at risk Participants received pemetrexed 500 milligrams per meter squared (mg/m\^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21 day cycle until disease progression or unacceptable toxicity developed up to 39 months.	Erlotinib n=83 participants at risk Participants received erlotinib 150 mg, administered orally once daily in each 21 day cycle until disease progression or unacceptable toxicity developed up to 39 months.	Pemetrexed n=80 participants at risk Participants received pemetrexed 500 mg/m\^2 of body surface area, administered by intravenous (IV) infusion on Day 1 of each 21 day cycle until progression or unacceptable toxicity developed up to 39 months.
Gastrointestinal disorders Abdominal pain upper	7.7% 6/78 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	13.3% 11/83 • Number of events 20 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.5% 6/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Constipation	12.8% 10/78 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.4% 7/83 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.0% 8/80 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Diarrhoea	37.2% 29/78 • Number of events 65 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	34.9% 29/83 • Number of events 70 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.0% 8/80 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Dyspepsia	6.4% 5/78 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.4% 7/83 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Mouth ulceration	5.1% 4/78 • Number of events 8 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.2% 6/83 • Number of events 8 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Nausea	26.9% 21/78 • Number of events 40 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	12.0% 10/83 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	21.2% 17/80 • Number of events 24 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Stomatitis	19.2% 15/78 • Number of events 49 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.8% 9/83 • Number of events 15 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Vomiting	32.1% 25/78 • Number of events 37 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	12.0% 10/83 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	15.0% 12/80 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Asthenia	15.4% 12/78 • Number of events 16 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.2% 6/83 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.5% 6/80 • Number of events 22 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Chest pain	5.1% 4/78 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	14.5% 12/83 • Number of events 12 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Fatigue	25.6% 20/78 • Number of events 33 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.8% 9/83 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	21.2% 17/80 • Number of events 24 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Mucosal inflammation	17.9% 14/78 • Number of events 27 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.4% 7/83 • Number of events 8 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Oedema	3.8% 3/78 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	5.0% 4/80 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Oedema peripheral	10.3% 8/78 • Number of events 24 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.5% 6/80 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
General disorders Pyrexia	14.1% 11/78 • Number of events 21 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	11.2% 9/80 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Herpes zoster	6.4% 5/78 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Paronychia	9.0% 7/78 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	16.9% 14/83 • Number of events 16 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Upper respiratory tract infection	9.0% 7/78 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	4.8% 4/83 • Number of events 8 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Infections and infestations Urinary tract infection	5.1% 4/78 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Alanine aminotransferase increased	16.7% 13/78 • Number of events 19 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.0% 8/80 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Aspartate aminotransferase increased	15.4% 12/78 • Number of events 19 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.8% 7/80 • Number of events 8 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Creatinine renal clearance decreased	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.5% 6/80 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Haemoglobin decreased	12.8% 10/78 • Number of events 21 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	4.8% 4/83 • Number of events 13 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Neutrophil count decreased	20.5% 16/78 • Number of events 70 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.8% 7/80 • Number of events 21 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Platelet count decreased	7.7% 6/78 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 20 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations Weight decreased	5.1% 4/78 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.4% 7/83 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Investigations White blood cell count decreased	20.5% 16/78 • Number of events 77 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 15 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.0% 8/80 • Number of events 17 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Decreased appetite	29.5% 23/78 • Number of events 39 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	18.1% 15/83 • Number of events 24 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	23.8% 19/80 • Number of events 31 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Hyperglycaemia	10.3% 8/78 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	4.8% 4/83 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.8% 7/80 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Metabolism and nutrition disorders Hyponatraemia	6.4% 5/78 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	4.8% 4/83 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.5% 6/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	5.1% 4/78 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Back pain	3.8% 3/78 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	9.6% 8/83 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	11.2% 9/80 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Myalgia	5.1% 4/78 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Anaemia	14.1% 11/78 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.8% 7/80 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Leukopenia	7.7% 6/78 • Number of events 27 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 13 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Lymphopenia	17.9% 14/78 • Number of events 26 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.0% 8/80 • Number of events 21 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Blood and lymphatic system disorders Neutropenia	15.4% 12/78 • Number of events 87 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	8.8% 7/80 • Number of events 30 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Eye disorders Blepharitis	5.1% 4/78 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	13.3% 11/83 • Number of events 16 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Eye disorders Conjunctivitis	5.1% 4/78 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Eye disorders Lacrimation increased	5.1% 4/78 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	4.8% 4/83 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	5.0% 4/80 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Eye disorders Vision blurred	1.3% 1/78 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.0% 5/83 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Gastrointestinal disorders Abdominal pain	6.4% 5/78 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.0% 5/83 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.8% 3/80 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	6.4% 5/78 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.0% 5/83 • Number of events 8 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	5.0% 4/80 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Dizziness	12.8% 10/78 • Number of events 12 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Headache	17.9% 14/78 • Number of events 16 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	9.6% 8/83 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Paraesthesia	5.1% 4/78 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Nervous system disorders Peripheral sensory neuropathy	3.8% 3/78 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/83 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Psychiatric disorders Insomnia	12.8% 10/78 • Number of events 18 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	12.0% 10/83 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.2% 5/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	19.2% 15/78 • Number of events 18 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	33.7% 28/83 • Number of events 32 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	16.2% 13/80 • Number of events 17 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.8% 10/78 • Number of events 12 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	12.0% 10/83 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	12.5% 10/80 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.6% 2/78 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	9.6% 8/83 • Number of events 11 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.4% 5/78 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Productive cough	6.4% 5/78 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.2% 6/83 • Number of events 7 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.1% 4/78 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	15.7% 13/83 • Number of events 21 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Acne	7.7% 6/78 • Number of events 10 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	3.6% 3/83 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Alopecia	11.5% 9/78 • Number of events 9 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 4 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Dermatitis acneiform	12.8% 10/78 • Number of events 19 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	6.0% 5/83 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Dry skin	15.4% 12/78 • Number of events 15 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	30.1% 25/83 • Number of events 26 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.5% 2/80 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Nail disorder	3.8% 3/78 • Number of events 3 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.2% 6/83 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	1.2% 1/80 • Number of events 1 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Pruritus	21.8% 17/78 • Number of events 25 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	24.1% 20/83 • Number of events 35 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	5.0% 4/80 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Rash	52.6% 41/78 • Number of events 57 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	51.8% 43/83 • Number of events 52 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	10.0% 8/80 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Skin exfoliation	6.4% 5/78 • Number of events 5 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	14.5% 12/83 • Number of events 14 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	0.00% 0/80 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/78 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	2.4% 2/83 • Number of events 2 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.	7.5% 6/80 • Number of events 6 One participant was assigned to Pemetrexed (single therapy) but received Erlotinib (single therapy) at the first cycle, this leads to the discrepancy of participants for the safety analysis.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60