CompletedNCT00949650Updated Apr 6, 2018Results posted

BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

A Phase 3 interventional study of Pemetrexed and BIBW 2992 in Carcinoma, Non-Small-Cell Lung and Adenocarcinoma, sponsored by Boehringer Ingelheim. Completed at 133 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-04-06.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 345
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.

Conditions studied

Carcinoma, Non-Small-Cell Lung
Adenocarcinoma

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In context

Adenocarcinoma

2,004 studies on the registry are indexed under Adenocarcinoma; 374 are open to participants now.

This study's enrollment of 345 is above the median of 45 across 1,553 interventional studies indexed under Adenocarcinoma.

Browse Adenocarcinoma studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material.
Measurable disease according to RECIST 1.1.
Eastern Cooperative Oncology Group score of 0 or 1.
Age >/= 18 years.
Life expectancy of at least three months.
Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice guidelines.

Exclusion criteria

Exclusion criteria:

Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies.
Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation.
Active brain metastases
Any other current malignancy or malignancy diagnosed within the past five years
Known pre-existing interstitial lung disease.
Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom.
History or presence of clinically relevant cardiovascular abnormalities.
Any other concomitant serious illness or organ system dysfunction.
Adequate absolute neutrophil count and platelet count
Adequate liver and kidney function
Active hepatitis B infection, active hepatitis C infection or known HIV carrier.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 345 participants (actual)

Study arms

Experimental
BIBW 2992
BIBW 2992 tablet once daily until progression
Drug: BIBW 2992
Active comparator
Cisplatin/Pemetrexed
Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles
Drug: Pemetrexed · Drug: Cisplatin

Interventions

DrugPemetrexed
Pemetrexed IV given once every 3 weeks for up to 6 cycles
DrugBIBW 2992
BIBW 2992 once daily until progression
DrugCisplatin
Cisplatin IV given once every 3 weeks for up to 6 cycles

What researchers measure

Primary outcomes

Progression-Free Survival (PFS) Time
PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression

Secondary outcomes

Percentage of Patients With Objective Response (OR)
OR was defined as Complete Response (CR) or Partial Response (PR). Assessed by central independent review according to RECIST 1.1.
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Percentage of Participants With Disease Control (DC)
DC was defined as a patient with OR or Stable Disease (SD). Assessed by central independent review according to the RECIST 1.1.
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Overall Survival (OS) Time
OS was defined as time from randomisation to death.
Time frame: From randomisation to cut-off date (17MAR2017).
Tumour Shrinkage
Tumour shrinkage was calculated as the minimum Sum of Diameters (SoD) of target lesions from all post-baseline tumour assessments, as read by the central independent review. The mean of these minimum values were presented after adjusting for baseline SoD, EGFR mutation group and race.
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Change From Baseline in Body Weight
Because the PFS was longer for patients in the Afatinib arm than for patients in the chemotherapy arm, the period of data collection for ECOG status and body weight continued for a longer time in the Afatinib arm.
Time frame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
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 self-care, unable to carry out any work activities. 3. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours. 4. Completely disabled, cannot carry on any self-care, totally confined to bed or chair. 5. Dead.
Time frame: Throughout the trial until progression (every 3 weeks), up to 28 months.
Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
HRQOL was measured by European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and its lung cancer specific module LC13 (QLQ-LC13). Analysis for cough is based on QLQ-LC13 question 1. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Time frame: Throughout the trial until progression (every 3 weeks).
HRQOL: Time to Deterioration in Dyspnoea
HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for dyspnoea is based on composite of QLQ-LC13 questions 3-5. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Time frame: Throughout the trial until progression (every 3 weeks).
HRQOL: Time to Deterioration in Pain
HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for pain is based on composite of QLQ-C30 questions 9 and 19. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Time frame: Throughout the trial until progression (every 3 weeks).
Trough Plasma Concentrations of Afatinib at Day 22
Trough plasma concentrations of Afatinib at Day 22 (course 2, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Time frame: Day 22.
Trough Plasma Concentrations of Afatinib at Day 29
Trough plasma concentrations of Afatinib at day 29 (course 2, visit 2) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Time frame: Day 29.
Trough Plasma Concentrations of Afatinib at Day 43
Trough plasma concentrations of Afatinib at Day 43 (course 3, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Time frame: Day 43.

Results

Posted Nov 19, 2013

Participant flow

Participant flow — Overall Study
Milestone	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Started	230	115
Completed	0	0
Not completed	230	115
Withdrew: Progressive disease	188	19
Withdrew: Completed 6 courses of chemotherapy	0	60
Withdrew: Other adverse event (ae)	28	17
Withdrew: Protocol violation	1	4
Withdrew: Refusal to continue medication	7	11
Withdrew: Not treated	1	4
Withdrew: Other not specified above	5	0

Outcome measures

PrimaryProgression-Free Survival (PFS) Time

PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.

Time frame:: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Reported as:: Median · Months.

Progression-Free Survival (PFS) Time
Months.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Progression-Free Survival (PFS) Time	11.17 (9.63 to 13.70)	6.90 (5.39 to 8.25)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Log Rank · p = 0.0002 (Two-sided p-value from log-rank test stratified by EGFR mutation group and race.)
Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Cox · p = 0.0002 · Hazard ratio (hr): 0.576 · 95% CI 0.426 to 0.778Afatinib 40 mg versus Pemetrexed/Cisplatin Chemotherapy.

SecondaryPercentage of Patients With Objective Response (OR)

OR was defined as Complete Response (CR) or Partial Response (PR). Assessed by central independent review according to RECIST 1.1.

Time frame:: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Reported as:: Number · Percentage of patients with OR.

Percentage of Patients With Objective Response (OR)
Percentage of patients with OR.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Percentage of Patients With Objective Response (OR)	56.5 (49.8 to 63.0)	22.6 (15.3 to 31.3)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Logistic · p = <0.0001 · Odds ratio (or): 4.802 · 95% CI 2.855 to 8.075Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.

SecondaryPercentage of Participants With Disease Control (DC)

DC was defined as a patient with OR or Stable Disease (SD). Assessed by central independent review according to the RECIST 1.1.

Time frame:: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Reported as:: Number · Percentage of participants with DC.

Percentage of Participants With Disease Control (DC)
Percentage of participants with DC.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Percentage of Participants With Disease Control (DC)	90.4 (85.9 to 93.9)	80.9 (72.5 to 87.6)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Logistic · p = 0.0118 · Odds ratio (or): 2.288 · 95% CI 1.202 to 4.356Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.

SecondaryOverall Survival (OS) Time

OS was defined as time from randomisation to death.

Time frame:: From randomisation to cut-off date (17MAR2017).
Reported as:: Median · Months.

Overall Survival (OS) Time
Months.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Overall Survival (OS) Time	28.16 (24.64 to 33.58)	28.22 (20.73 to 33.22)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Log Rank · p = 0.7916 (Two-sided p-value from log-rank test stratified by EGFR mutation group and race.)
Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Cox · p = 0.3850 · Hazard ratio (hr): 0.880 · 95% CI 0.660 to 1.174Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.

SecondaryTumour Shrinkage

Tumour shrinkage was calculated as the minimum Sum of Diameters (SoD) of target lesions from all post-baseline tumour assessments, as read by the central independent review. The mean of these minimum values were presented after adjusting for baseline SoD, EGFR mutation group and race.

Time frame:: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Reported as:: Mean · mm.

Tumour Shrinkage
mm.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Tumour Shrinkage	33.19 ± 1.12	43.00 ± 1.59

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · ANCOVA · p = <0.0001 · Mean difference (final values): -9.82 · 95% CI -13.64 to -5.99Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.

SecondaryChange From Baseline in Body Weight

Because the PFS was longer for patients in the Afatinib arm than for patients in the chemotherapy arm, the period of data collection for ECOG status and body weight continued for a longer time in the Afatinib arm.

Time frame:: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
Reported as:: Mean · Kg.

Change From Baseline in Body Weight
Kg.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Change from baseline at lowest value	-3.95 ± 3.91	-2.68 ± 2.90
Change from baseline at last value	-1.19 ± 5.36	-0.29 ± 4.02

SecondaryEastern Cooperative Oncology Group (ECOG) Performance Status (PS)

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 self-care, unable to carry out any work activities. 3. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours. 4. Completely disabled, cannot carry on any self-care, totally confined to bed or chair. 5. Dead.

Time frame:: Throughout the trial until progression (every 3 weeks), up to 28 months.
Reported as:: Number · Participants

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Participants	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
ECOG PS 0 (last value)	92	41
ECOG PS 1 (last value)	138	73
ECOG PS 2 (last value)	0	1

SecondaryHealth Related Quality of Life (HRQOL): Time to Deterioration in Coughing

HRQOL was measured by European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and its lung cancer specific module LC13 (QLQ-LC13). Analysis for cough is based on QLQ-LC13 question 1. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.

Time frame:: Throughout the trial until progression (every 3 weeks).
Reported as:: Median · Months.

Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
Months.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing	26.97 (19.22 to NA)	8.02 (4.44 to NA)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Log Rank · p = 0.0062 (Two-sided p-value from log-rank test stratified by EGFR mutation group and race.)
Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Cox · p = 0.2133 · Hazard ratio (hr): 0.589 · 95% CI 0.401 to 0.866Afatinib 40 mg vs. Pemetrexed/Cisplatin Chemotherapy, if HR\<1 then favours Afatinib 40 mg.

SecondaryHRQOL: Time to Deterioration in Dyspnoea

HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for dyspnoea is based on composite of QLQ-LC13 questions 3-5. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.

Time frame:: Throughout the trial until progression (every 3 weeks).
Reported as:: Median · Months.

HRQOL: Time to Deterioration in Dyspnoea
Months.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
HRQOL: Time to Deterioration in Dyspnoea	10.41 (5.59 to 15.93)	2.86 (2.17 to 4.90)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Log Rank · p = 0.0129 (Two-sided p-value from log-rank test stratified by EGFR mutation group and race.)
Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Cox · p = 0.0078 · Hazard ratio (hr): 0.680 · 95% CI 0.499 to 0.927Afatinib 40 mg vs. Pemetrexed/Cisplatin Chemotherapy, if HR\<1 then favours Afatinib 40 mg.

SecondaryHRQOL: Time to Deterioration in Pain

HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for pain is based on composite of QLQ-C30 questions 9 and 19. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.

Time frame:: Throughout the trial until progression (every 3 weeks).
Reported as:: Median · Months.

HRQOL: Time to Deterioration in Pain
Months.	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
HRQOL: Time to Deterioration in Pain	4.17 (2.79 to 5.59)	3.09 (2.17 to 3.98)

Statistical analysis

Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Log Rank · p = 0.1882 (Two-sided p-value from log-rank test stratified by EGFR mutation group and race.)
Afatinib 40 mg vs Pemetrexed/Cisplatin Chemotherapy · Regression, Cox · p = 0.0427 · Hazard ratio (hr): 0.826 · 95% CI 0.618 to 1.104Afatinib 40 mg vs. Pemetrexed/Cisplatin Chemotherapy, if HR\<1 then favours Afatinib 40 mg.

SecondaryTrough Plasma Concentrations of Afatinib at Day 22

Trough plasma concentrations of Afatinib at Day 22 (course 2, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.

Time frame:: Day 22.
Reported as:: Geometric mean · ng/mL.

Trough Plasma Concentrations of Afatinib at Day 22
ng/mL.	Afatinib 20 mg	Afatinib 30 mg	Afatinib 40 mg	Afatinib 50 mg
Trough Plasma Concentrations of Afatinib at Day 22	—	21.8 ± 36.6	28.0 ± 85.0	29.9 ± 46.1

SecondaryTrough Plasma Concentrations of Afatinib at Day 29

Trough plasma concentrations of Afatinib at day 29 (course 2, visit 2) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.

Time frame:: Day 29.
Reported as:: Geometric mean · ng/mL.

Trough Plasma Concentrations of Afatinib at Day 29
ng/mL.	Afatinib 20 mg	Afatinib 30 mg	Afatinib 40 mg	Afatinib 50 mg
Trough Plasma Concentrations of Afatinib at Day 29	—	28.0 ± 82.4	25.8 ± 69.5	29.6 ± 79.2

SecondaryTrough Plasma Concentrations of Afatinib at Day 43

Trough plasma concentrations of Afatinib at Day 43 (course 3, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.

Time frame:: Day 43.
Reported as:: Geometric mean · ng/mL.

Trough Plasma Concentrations of Afatinib at Day 43
ng/mL.	Afatinib 20 mg	Afatinib 30 mg	Afatinib 40 mg	Afatinib 50 mg
Trough Plasma Concentrations of Afatinib at Day 43	24.4 ± 260	24.7 ± 63.9	23.5 ± 66.2	27.5 ± 64.4

Adverse events

Collected over First administration of trial medication until 28 days after last administration of trial medication.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Afatinib 40 mg	—	72/229 (31.4%)	229/229 (100%)
Pemetrexed/Cisplatin Chemotherapy	—	25/111 (22.5%)	108/111 (97.3%)

Most frequent serious events

Showing 10 of 94

Most frequent serious events
Event	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
DiarrhoeaGastrointestinal disorders	15/229	0/111
VomitingGastrointestinal disorders	11/229	3/111
Pleural effusionRespiratory, thoracic and mediastinal disorders	2/229	3/111
AnaemiaBlood and lymphatic system disorders	0/229	2/111
NauseaGastrointestinal disorders	0/229	2/111
AstheniaGeneral disorders	1/229	2/111
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	3/229	2/111
DyspnoeaRespiratory, thoracic and mediastinal disorders	4/229	2/111
PneumoniaInfections and infestations	4/229	1/111
HypokalaemiaMetabolism and nutrition disorders	4/229	1/111

Most frequent other events

Showing 10 of 68

Most frequent other events
Event	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy
DiarrhoeaGastrointestinal disorders	216/229	25/111
NauseaGastrointestinal disorders	65/229	75/111
RashSkin and subcutaneous tissue disorders	145/229	11/111
ParonychiaInfections and infestations	132/229	0/111
Decreased appetiteMetabolism and nutrition disorders	70/229	61/111
VomitingGastrointestinal disorders	53/229	50/111
StomatitisGastrointestinal disorders	88/229	10/111
ConstipationGastrointestinal disorders	37/229	39/111
FatigueGeneral disorders	45/229	39/111
NeutropeniaBlood and lymphatic system disorders	4/229	35/111

Baseline characteristics

Randomised Set (RS): The randomised set includes all patients who were randomised to receive treatment, whether treated or not.

Age, Continuous
Age, Continuous(Years)	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy	Total
Mean	60.5 ± 10.1	59.9 ± 10.0	60.3 ± 10.1

Sex: Female, Male
Sex: Female, Male(Participants)	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy	Total
Female	147	77	224
Male	83	38	121

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy	Total
Asian	166	83	249
Non-Asian	64	32	96

Epidermal Growth Factor Receptor (EGFR) mutation group
Epidermal Growth Factor Receptor (EGFR) mutation group(Participants)	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy	Total
EGFR mutation category: L858R	91	47	138
EGFR mutation category: Deletion Exon 19	112	57	169
EGFR mutation category: Other	27	11	38

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)(Participants)	Afatinib 40 mg	Pemetrexed/Cisplatin Chemotherapy	Total
ECOG PS 0 (baseline)	92	41	133
ECOG PS 1 (baseline)	138	73	211
ECOG PS 2 (baseline)	0	1	1

Study locations

133 sites

Highlands Oncology Group
Fayetteville, Arkansas 72703, United States
Clinical Trials and Research Associates Inc
Montebello, California 90640, United States
Innovative Medical Research of South Florida
Miami, Florida 33179, United States
Crescent City Research Consortiom
Marrero, Louisiana 70072, United States
Interlakes Foundation, Incorporated
Rochester, New York 14623, United States
Lehigh Valley Hospital / Lehigh Valley Health Network
Allentown, Pennsylvania 18103, United States
South Texas Institute of Cancer, Northwest Cancer Center
Corpus Christi, Texas 78410, United States
Instituto de Medicina Nuclear de Bahía Blanca
Bahía Blanca, B8000FJI, Argentina
Hospital Alemán
Capital Federal, C1118AAT, Argentina
Imcaba S.R.L.
Capital Federal, C1185AAT, Argentina
IMAI Research
Capital Federal, C1425AWC, Argentina
Instituto Alexander Fleming
Capital Federal, C1426ANZ, Argentina
Hospital Militar Central
Capital Federal, C1426BOR, Argentina
PALIAR
Capital Federal, C1430ERF, Argentina
Centro Oncológico de Rosario
Rosario, S2000KZE, Argentina
Lifehouse
Camperdown, New South Wales 2050, Australia
Royal North Shore Hospital
St Leonards, New South Wales 2065, Australia
Calvary Mater Newcastle Hospital
Waratah, New South Wales 2298, Australia
The Prince Charles Hospital
Chermside, Queensland 4032, Australia
Flinders Medical Centre
Bedford Park, South Australia 5042, Australia
The Burnside War Memorial Hospital
Toorak Gardens, South Australia 5065, Australia
Box Hill Hospital
Box Hill, Victoria 3128, Australia
St. Vincents Hospital (MEL)
Fitzroy, Victoria 3065, Australia
Mount Medical Centre
Perth, Western Australia 6000, Australia
KH d. Elisabethinen Linz
Linz, 4010, Austria
Klinikum Wels - Grieskirchen GmbH
Wels, 4600, Austria
SMZ Baumgartner Hoehe Otto Wagner Spital
Wien, 1140, Austria
Brussels - UNIV St-Pierre
Bruxelles, 1000, Belgium
UNIV UZ Gent
Gent, 9000, Belgium
Brussels - UNIV UZ Brussel
Jette, 1090, Belgium
UZ Leuven
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
Centro de Pesquisa do Hospital Lifecenter
Belo Horizonte, Brazil
Centro de Pesquisas Clínicas em Oncología
Cachoeiro de Itapemirim, 29308-014, Brazil
Insituto de Oncologia do Paraná
Curitiba, 80530-010, Brazil
Hospital São Lucas da Pontifícia Universidade Católica
Porto Alegre, 90610-000, Brazil
UNIFESP Departamento de Medicina de Pneumologia
Sao Paulo, 04023-900, Brazil
Tom Baker Cancer Centre
Calgary, Alberta T2N 4N2, Canada
Cross Cancer Institute (University of Alberta)
Edmonton, Alberta T6G 1Z2, Canada
Charles LeMoyne Hospital
Greenfield Park, Migration Data J4V 2H1, Canada
Hematologiste et oncologue medical CHUM - Hopital Notre-Dame
Montreal, Migration Data H2L 4M1, Canada
McGill University, Department of Oncology
Montreal, Migration Data H2W 1S6, Canada
Hospital Dirección de Previsión de Carabineros
Los Condes, 760-0746, Chile
Instituto Oncológico Limitada Viña del Mar
Reñaca, 2540364, Chile
Instituto Clínico Oncológico del Sur - ICOS
Temuco, Chile
HOP d'Angers
Angers, 49933, France
HOP Côte de Nacre
Caen Cedex 5, 14033, France
HOP Nord Michallon
La Tronche, 38700, France
HOP Croix Rousse, Pneumo, Lyon
Lyon Cedex 4, 69317, France
INS Curie
Paris Cedex 05, 75248, France
CTR René Gauducheau
Saint Herblain, 44805, France
HOP Sud-Réunion, Pneumo, Saint Pierre
Saint Pierre - La Réunion, 97448, France
HOP - HIA Sainte Anne
Toulon, 83041, France
HOP, Pneumo, Villefranche sur Saône
Villefranche Sur Saône, 69655, France
Universitätsklinikum Benjamin Franklin, Berlin
Berlin, 12200, Germany
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
Essen, 45122, Germany
Medizinische Hochschule Hannover
Hannover, 30625, Germany
Lungenklinik Hemer
Hemer, 58675, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55101, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Pius-Hospital, Oldenburg
Oldenburg, 26121, Germany
National Taiwan University Hospital
Taipei, 100, Germany
Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales Hospital
Shatin, Hong Kong
Szent György Hospital, Szekesfehervar
Szekesfehervar, 8000, Hungary
Markusovszky County Hospital, Szombathely
Szombathely, 9700, Hungary
Zala County Hospital, Zalaegerszeg
Zalaegerszeg, 8900, Hungary
St James's Hospital
Dublin 8, Ireland
Ospedale San Donato di Arezzo
Arezzo, 52100, Italy
Az. USL 4 di Prato
Prato, 59100, Italy
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
Roma, 00189, Italy
Osp. Silvestrin
Sant'Andrea Delle Fratte (PG), 06132, Italy
National Hospital Organization Nagoya Medical Center
Aichi, Nagoya, 460-0001, Japan
Aichi Cancer Center Hospital
Aichi, Nagoya, 464-8681, Japan
National Cancer Center Hospital East
Chiba, Kashiwa, 277-8577, Japan
National Hospital Organization Shikoku Cancer Center
Ehime, Matsuyama, 791-0280, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395, Japan
Hokkaido University Hospital
Hokkaido, Sapporo, 060-8648, Japan
Institute of Biomedical Research and Innovation Hospital
Hyogo, Kobe, 650-0047, Japan
Kanazawa University Hospital
Ishikawa, Kanazawa, 920-8641, Japan
Kanagawa Cardiovascular and Respiratory Center
Kanagawa, Yokohama, 236-0051, Japan
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566, Japan
Kurashiki Central Hospital
Okayama, Kurashiki, 710-8602, Japan
Okayama University Hospital
Okayama, Okayama, 700-8558, Japan
Kindai University Hospital
Osaka, Osaka-Sayama, 589-8511, Japan
Osaka City Hospital Organization Osaka City General Hospital
Osaka, Osaka, 534-0021, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakai, Osaka, 591-8555, Japan
Shizuoka Cancer Center
Shizuoka, Sunto-gun, 411-8777, Japan
Chungbuk National University Hospital
Cheongju, 361-771, Korea, Republic of
Chonnam National University Hwasun Hospital
Hwasun, 519-763, Korea, Republic of
Seoul National University Bundang Hospital
Seongnam, 13620, Korea, Republic of
Asan Medical Center
Seoul, 138-736, Korea, Republic of
Ulsan University Hospital
Ulsan, 682-714, Korea, Republic of
Hospital Pulau Pinang
Palau Pinang, 10990, Malaysia
Pusat Perubatan University Kebangsaan Malaysia
Wilayah Persekutuan, 5600, Malaysia
University Malaya Medical Centre
Wilayah Persekutuan, 59100, Malaysia
Hospital Nacional Guillermo Almenara Irigoyen
La Victoria, Peru
Clínica Anglo Americana
San Isidro, 27, Peru
Instituto Nacional de Enfermedades Neoplásicas
Surquillo, 34, Peru
Perpetual Succour Hospital (Cebu)
Cebu City, 6000, Philippines

Showing the first 100 of 133 sites across 25 countries.

References and documents

Publications

Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, Lee KH, Tsai CM, Kato T, Barrios CH, Schuler M, Hirsh V, Yamamoto N, O'Byrne K, Boyer M, Mok T, Peil B, Marten A, Chih-Hsin Yang J, Paz-Ares L, Park K. Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials. Clin Lung Cancer. 2018 Jul;19(4):e465-e479. doi: 10.1016/j.cllc.2018.03.009. Epub 2018 Mar 17. PubMed 29653820 ↗
Yang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O'Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016 Nov;27(11):2103-2110. doi: 10.1093/annonc/mdw322. Epub 2016 Sep 6. PubMed 27601237 ↗
Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. doi: 10.1016/j.jtho.2015.11.014. Epub 2016 Jan 25. PubMed 26823294 ↗
Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 2015 Sep;106(9):1202-11. doi: 10.1111/cas.12723. Epub 2015 Jul 25. PubMed 26094656 ↗
Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4. PubMed 26051236 ↗
Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. doi: 10.1016/S1470-2045(14)71173-8. Epub 2015 Jan 12. PubMed 25589191 ↗
Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. doi: 10.1200/JCO.2012.46.1764. Epub 2013 Jul 1. PubMed 23816967 ↗
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1. PubMed 23816960 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00949650
Lead sponsor: Boehringer Ingelheim
Responsible party: Sponsor
First posted: Jul 30, 2009
Start date: Aug 14, 2009
Primary completion: Feb 9, 2012
Completion: Mar 16, 2017
Results posted: Nov 19, 2013
Last update: Apr 6, 2018

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Boehringer Ingelheim

study chair · Boehringer Ingelheim

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BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

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