Trial Outcomes & Findings for BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC) (NCT NCT01121393)

Last Updated: 2018-12-14

Results Overview

The primary endpoint was progression-free survival (PFS) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival was defined as the time from randomisation to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not have a PFS. Only data collected up until the analysis cut-off date (27 December 2013) were considered. Median time results from unstratified Kaplan-Meier estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

364 participants

Primary outcome timeframe

Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 168

Results posted on

2018-12-14

Participant Flow

Two-arm, randomised (2:1 ratio), open-label, active-controlled, parallel-group comparison of afatinib versus gemcitabine / cisplatin chemotherapy.

All patients were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they met all strictly implemented inclusion/exclusion criteria. Patients were not to be entered to trial treatment if any one of the specific entry criteria was violated.

Participant milestones

Participant milestones
Measure	Afatinib 40 Milligram (mg) Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.
Overall Study STARTED	242	122
Overall Study Treated	239	113
Overall Study COMPLETED	0	38
Overall Study NOT COMPLETED	242	84

Reasons for withdrawal

Reasons for withdrawal
Measure	Afatinib 40 Milligram (mg) Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.
Overall Study Progressive disease	201	20
Overall Study Other Adverse events	24	45
Overall Study Non-compliant with protocol	0	3
Overall Study Lost to Follow-up	1	0
Overall Study Refused cont. medication	7	7
Overall Study Not treated	3	9
Overall Study Other than listed	6	0

Baseline Characteristics

Treated Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Total n=364 Participants Total of all reporting groups
Age, Continuous	56.7 Years STANDARD_DEVIATION 11.2 • n=242 Participants • Treated Set	55.6 Years STANDARD_DEVIATION 10.1 • n=122 Participants • Treated Set	56.4 Years STANDARD_DEVIATION 10.9 • n=364 Participants • Treated Set
Sex: Female, Male Female	155 Participants n=242 Participants	83 Participants n=122 Participants	238 Participants n=364 Participants
Sex: Female, Male Male	87 Participants n=242 Participants	39 Participants n=122 Participants	126 Participants n=364 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Epidermal growth factor receptor (EGFR) L858R (L858R alone and L858R + Deletion Exon 19)	92 Participants n=242 Participants	46 Participants n=122 Participants	138 Participants n=364 Participants
Epidermal growth factor receptor (EGFR) Deletion Exon 19 (alone)	124 Participants n=242 Participants	62 Participants n=122 Participants	186 Participants n=364 Participants
Epidermal growth factor receptor (EGFR) Other	26 Participants n=242 Participants	14 Participants n=122 Participants	40 Participants n=364 Participants
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ECOG PS 0 (baseline)	48 Participants n=242 Participants	41 Participants n=122 Participants	89 Participants n=364 Participants
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ECOG PS 1 (baseline)	194 Participants n=242 Participants	81 Participants n=122 Participants	275 Participants n=364 Participants

PRIMARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 168

Population: The randomised set (RS) included all patients randomised to receive treatment, whether treated or not.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Progression-free Survival	11.01 months Interval 9.66 to 13.73	5.59 months Interval 4.67 to 6.7	—

SECONDARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Population: The randomised set.

OR is defined as a best overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with OR. CR is defined as the disappearance of all target lesions and non-target lesions and no new lesions. PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD, non-Progressive Disease or non evaluation of all non-target lesions and no new lesions. (Exact 95% Confidence interval by Clopper and Pearson.)

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Objective Response (OR)	67.8 percentage of participants Interval 61.5 to 73.6	23.0 percentage of participants Interval 15.8 to 31.4	—

SECONDARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Population: The randomised set.

DC is defined as a patient with objective response (OR) or stable disease (SD) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with DC.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Disease Control (DC)	92.6 percentage of participants Interval 88.5 to 95.5	76.2 percentage of participants Interval 67.7 to 83.5	—

SECONDARY outcome

Timeframe: From randomisation up to 374 weeks

Population: The randomised set.

OS is defined as the time from randomisation to death. For patients who had not died until 7 December 2017, the date they were last known to be alive was derived from patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date. Median time results from unstratified Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Overall Survival (OS)	23.10 months Interval 20.4 to 27.33	23.46 months Interval 17.94 to 25.56	—

SECONDARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Population: The RS included all patients randomised to receive treatment, whether treated or not.

OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1. For patients with an objective response, time to objective response was defined as the time from randomisation to the first objective response. Outcome data are the percentage of patients with OR by each scheduled tumour assessment.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Time to Objective Response (OR) By Week 24	64.9 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 6	49.2 percentage of participants	13.1 percentage of participants	—
Time to Objective Response (OR) By Week 12	59.9 percentage of participants	19.7 percentage of participants	—
Time to Objective Response (OR) By Week 18	64.0 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 30	65.7 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 36	66.1 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 42	66.5 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 48	66.5 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 60	66.9 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 72	66.9 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 84	66.9 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 96	67.4 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 108	67.4 percentage of participants	23.0 percentage of participants	—
Time to Objective Response (OR) By Week 120	67.8 percentage of participants	23.0 percentage of participants	—

SECONDARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Population: The Randomised set with an objective response.

OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1. For patients with an objective response, duration of objective response was defined as the time from the first objective response to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=164 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=28 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Duration of Objective Response	9.72 months Interval 8.34 to 12.45	4.27 months Interval 2.76 to 5.75	—

SECONDARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Population: The randomised set with disease control.

For patients with disease control, duration of disease control was defined as the time from randomisation to progression or death whichever occurs first. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=224 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=93 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Duration of Disease Control	11.07 months Interval 9.69 to 13.8	5.65 months Interval 5.49 to 6.93	—

SECONDARY outcome

Timeframe: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Population: The randomised set. There were ony 220 patients in the Afatinib arm and 101 patients in the Gemcitabine / Cisplatin arm with baseline and post-baseline target lesion measurements.

Tumour shrinkage is calculated as the minimum post-baseline sum of longest diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) (SLD), as assessed by central independent review. The mean of these minimum values are presented after adjusting for baseline sum of longest diameters and EGFR mutation category. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered. A negative value means the smallest post-baseline SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline. The means are adjusted for baseline sum of lesions and EGFR mutation category.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=220 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=101 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Tumour Shrinkage	33.41 millimetre (mm) Standard Error 0.99	47.06 millimetre (mm) Standard Error 1.45	—

SECONDARY outcome

Timeframe: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

Population: The randomised set. Data only presented for a patient with a baseline and at least on post-baseline assessment of weight.

The change from baseline to the lowest and the last body weight recorded or during the the study.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=237 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=109 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Change From Baseline in Body Weight Change from baseline at lowest value	-3.03 kilogram (kg) Standard Deviation 3.99	-1.52 kilogram (kg) Standard Deviation 3.65	—
Change From Baseline in Body Weight Change from baseline at last value	-0.76 kilogram (kg) Standard Deviation 4.79	0.00 kilogram (kg) Standard Deviation 4.52	—

SECONDARY outcome

Timeframe: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

Population: The randomised set. Data only presented for patients with a baseline and at least one post-baseline assessment of ECOG status.

The last ECOG performance score category recorded during the study. Outcome data are the percentage of patients with an shift of ECOG performance status from baseline to the last ECOG performance status. ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work; 2. Ambulatory (\>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities; 3. Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours; 4. Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; 5. Dead

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=237 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=110 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0 (baseline) 1 (last value)	8.0 percentage of participants	14.5 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1 (baseline) 1 (last value)	67.5 percentage of participants	51.8 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0 (baseline) 2 (last value)	0.4 percentage of participants	0.0 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1 (baseline) 2 (last value)	2.1 percentage of participants	1.8 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0 (baseline) 3 (last value)	0.0 percentage of participants	0.0 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1 (baseline) 3 (last value)	2.1 percentage of participants	4.5 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0 (baseline) 4 (last value)	0.4 percentage of participants	0.0 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1 (baseline) 4 (last value)	1.3 percentage of participants	1.8 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0 (baseline) 0 (last value)	11.4 percentage of participants	21.8 percentage of participants	—
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1 (baseline) 0 (last value)	6.8 percentage of participants	3.6 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

Population: The randomised set.

HRQOL as measured by standardised questionnaires (EuropeanOrganisation for Research and Treatment of Cancer (EORTC)) quality of life questionaires (OLQ-C30) and its lung cancer module (QLQ-LC13). Analysis for cough: QLQ-LC13, question 1. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing	31.05 months Interval 17.45 to As only 84 patients (34.7 percent) in Afatinib 40mg deteriorated, the upper limit of the confidence interval was not estimable.	10.28 months Interval 4.63 to As only 39 patients (32.0 percent) in Gemcitabine / Cisplatin deteriorated, the upper limit of the confidence interval was not estimable.	—

SECONDARY outcome

Timeframe: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

Population: The randomised set.

HRQOL as measured by OLQ-C30 and its lung cancer module (QLQ-LC13). Analysis for dyspnoea: composite of QLQ-LC13, questions 3 to 5; individual item from QLQ-C30, question 8. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea	7.66 months Interval 4.76 to 11.17	1.68 months Interval 1.38 to 3.15	—

SECONDARY outcome

Timeframe: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

Population: The randomised set.

HRQOL as measured by OLQ-C30 and its lung cancer module QLQ-LC13. Analysis for pain: composite of QLQ-C30, questions 9 and 19; individual items from QLQ-LC13, questions 10, 11 and 12. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=242 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=122 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Health Related Quality of Life (HRQOL): Time of Deterioration in Pain	6.93 months Interval 4.21 to 10.38	3.38 months Interval 1.77 to 5.29	—

SECONDARY outcome

Timeframe: Day 22 (course 2, visit 1)

Population: All patients who had at least 1 afatinib dose and who had at least 1 valid afatinib plasma concentration available.

Outcome data are the trough plasma concentrations of afatinib at day 22 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the Pharmacokinetics (PK) assessment period).

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=3 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=210 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Pharmacokinetics of Afatinib at Day 22	17.7 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 109	23.1 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 65.1	—

SECONDARY outcome

Timeframe: Day 29 (course 2, visit 2)

Population: All patients who had at least 1 afatinib dose and who had at least 1 valid afatinib plasma concentration available.

Outcome data are the trough plasma concentrations of afatinib at day 29 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=6 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=161 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. n=34 Participants Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Pharmacokinetics of Afatinib at Day 29	19.5 ng/mL Geometric Coefficient of Variation 90.3	23.8 ng/mL Geometric Coefficient of Variation 70.6	22.8 ng/mL Geometric Coefficient of Variation 60.8

SECONDARY outcome

Timeframe: Day 43 (course 3, visit 1)

Population: All patients who had at least 1 afatinib dose and who had at least 1 valid afatinib plasma concentration available.

Outcome data are the trough plasma concentrations of afatinib at day 43 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=21 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=158 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. n=35 Participants Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Pharmacokinetics of Afatinib at Day 43	21.5 ng/mL Geometric Coefficient of Variation 52.9	22.1 ng/mL Geometric Coefficient of Variation 67.4	22.9 ng/mL Geometric Coefficient of Variation 62.5

SECONDARY outcome

Timeframe: From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.

Population: The treated set (TS) included all randomised patients who were documented to have taken at least 1 dose of study medication (i.e. afatinib or gemcitabine / cisplatin). Patients were allocated according to the treatment actually received.

Safety of Afatinib as indicated by intensity and incidence of adverse events graded according to the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Presented as the percentage of patients with an Adverse Events during the on-treatment period by highest CTCAE grade.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=239 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=113 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events CTCAE Grade 1	13.8 percentage of participants	8.0 percentage of participants	—
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events CTCAE Grade 2	36.0 percentage of participants	29.2 percentage of participants	—
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events CTCAE Grade 3	39.3 percentage of participants	38.1 percentage of participants	—
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events CTCAE Grade 4	4.2 percentage of participants	21.2 percentage of participants	—
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events CTCAE Grade 5	6.7 percentage of participants	2.7 percentage of participants	—

SECONDARY outcome

Timeframe: From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.

Population: Treated set (TS) included all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated according to the treatment actually received. Patients with a baseline and at least one on-treatment assessment of the parameter are of interest.

Outcome data presented are the percentage of patients by worst CTCAE grade (only Grades 2 to 4 presented) on treatment for the following laboratory parameters: Potassium, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine and Creatine Kinase. For Potassium; only CTCAE grades resulting from hypokalemia (low values) are presented.

Outcome measures

Outcome measures
Measure	Afatinib 40 Milligram (mg) n=239 Participants Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.	Gemcitabine / Cisplatin Chemotherapy n=113 Participants Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.	Afatinib 50mg q.d. Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.
Changes in Safety Laboratory Parameters Potassium CTCAE grade 2	NA percentage of participants no corresponding rules defined	NA percentage of participants no corresponding rules defined	—
Changes in Safety Laboratory Parameters Potassium CTCAE grade 3	5.1 percentage of participants	15.6 percentage of participants	—
Changes in Safety Laboratory Parameters Potassium CTCAE grade 4	2.6 percentage of participants	0.9 percentage of participants	—
Changes in Safety Laboratory Parameters AST CTCAE grade 2	5.1 percentage of participants	1.9 percentage of participants	—
Changes in Safety Laboratory Parameters AST CTCAE grade 3	1.3 percentage of participants	1.9 percentage of participants	—
Changes in Safety Laboratory Parameters AST CTCAE grade 4	0.0 percentage of participants	0.0 percentage of participants	—
Changes in Safety Laboratory Parameters ALT CTCAE grade 2	8.1 percentage of participants	5.6 percentage of participants	—
Changes in Safety Laboratory Parameters ALT CTCAE grade 3	3.4 percentage of participants	1.9 percentage of participants	—
Changes in Safety Laboratory Parameters ALT CTCAE grade 4	0.0 percentage of participants	0.0 percentage of participants	—
Changes in Safety Laboratory Parameters Creatinine CTCAE grade 2	2.1 percentage of participants	2.8 percentage of participants	—
Changes in Safety Laboratory Parameters Creatinine CTCAE grade 3	0.0 percentage of participants	0.0 percentage of participants	—
Changes in Safety Laboratory Parameters Creatinine CTCAE grade 4	0.0 percentage of participants	0.0 percentage of participants	—
Changes in Safety Laboratory Parameters Creatinine Kinase CTCAE grade 2	3.7 percentage of participants	1.0 percentage of participants	—
Changes in Safety Laboratory Parameters Creatinine Kinase CTCAE grade 3	1.9 percentage of participants	0.0 percentage of participants	—
Changes in Safety Laboratory Parameters Creatinine Kinase CTCAE grade 4	0.0 percentage of participants	0.0 percentage of participants	—

Adverse Events

Afatinib 40 Milligram (mg)

Serious events: 40 serious events

Other events: 236 other events

Deaths: 16 deaths

Gemcitabine / Cisplatin Chemotherapy

Serious events: 12 serious events

Other events: 112 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

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Boehringer Ingelheim

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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