Trial Outcomes & Findings for LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung (NCT NCT01466660)

Last Updated: 2020-04-07

Results Overview

Progression-free survival (PFS) defined as the time from date of randomisation to date of disease progression, or date of death if a patient died earlier. Participants with no event (Disease progression (PD) or death) were censored. PD was primarily evaluated for the primary analysis by an independent central imaging review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started, together with an absolute increase in the SoD of target lesions of at least 5 millimetre (mm) or the appearance of one or more new lesions. For the final analysis (analysis cut-off date 12 April 2019) status and date of PD were determined by investigator assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

319 participants

Primary outcome timeframe

From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.

Results posted on

2020-04-07

Participant Flow

Two-arm, randomised (1:1 ratio), open-label, parallel group trial. In the study disease response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Afatinib Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Study STARTED	160	159
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	160	159

Reasons for withdrawal

Reasons for withdrawal
Measure	Afatinib Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Study Progressive Disease (RECIST 1.1)	120	127
Overall Study Worsening of underlying cancer disease	5	2
Overall Study Other adverse event	19	18
Overall Study Protocol Violation	2	1
Overall Study Refused continuation of trial medication	4	3
Overall Study Other reason not defined above	10	8

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=159 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Total n=319 Participants Total of all reporting groups
Age, Continuous	61.7 Years STANDARD_DEVIATION 11.5 • n=160 Participants	63.0 Years STANDARD_DEVIATION 10.4 • n=159 Participants	62.4 Years STANDARD_DEVIATION 11.0 • n=319 Participants
Sex: Female, Male Female	91 Participants n=160 Participants	106 Participants n=159 Participants	197 Participants n=319 Participants
Sex: Female, Male Male	69 Participants n=160 Participants	53 Participants n=159 Participants	122 Participants n=319 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=160 Participants	0 Participants n=159 Participants	0 Participants n=319 Participants
Race (NIH/OMB) Asian	94 Participants n=160 Participants	88 Participants n=159 Participants	182 Participants n=319 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=160 Participants	0 Participants n=159 Participants	0 Participants n=319 Participants
Race (NIH/OMB) Black or African American	1 Participants n=160 Participants	0 Participants n=159 Participants	1 Participants n=319 Participants
Race (NIH/OMB) White	48 Participants n=160 Participants	54 Participants n=159 Participants	102 Participants n=319 Participants
Race (NIH/OMB) More than one race	0 Participants n=160 Participants	0 Participants n=159 Participants	0 Participants n=319 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=160 Participants	17 Participants n=159 Participants	34 Participants n=319 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.

Population: Randomised set which included all patients randomised to receive treatment, whether treated or not.

Outcome measures

Outcome measures
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=159 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Progression-free Survival	12.78 Months Interval 10.91 to 14.72	11.17 Months Interval 9.49 to 12.81

PRIMARY outcome

Timeframe: From first drug administration until last drug administration, up to 1482 days

Population: Randomised set which included all patients randomised to receive treatment, whether treated or not.

Time to Treatment Failure (TTF) which was the time from the date of randomisation to the date of i.e. permanent treatment discontinuation for any reason.

Outcome measures

Outcome measures
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=159 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Time to Treatment Failure (TTF) (Main Overall Survival Analysis Cut-off Date, 08 April 2016)	13.67 Months Interval 11.89 to 14.95	11.53 Months Interval 10.09 to 13.11

PRIMARY outcome

Timeframe: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on death, up to 2465 days.

Population: Randomised set which included all patients randomised to receive treatment, whether treated or not.

Overall survival (OS) which was defined as the time from the date of randomisation to the date of death. Participants for whom there is no evidence of death at the time of the analysis will be censored at the date that they were last known to be alive.

Outcome measures

Outcome measures
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=159 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Survival	27.86 Months Interval 25.13 to 32.85	24.54 Months Interval 20.57 to 28.88

SECONDARY outcome

Timeframe: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.

Population: Randomised set which included all patients randomised to receive treatment, whether treated or not.

Objective response rate (ORR) which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions from baseline. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.

Outcome measures

Outcome measures
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=159 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Objective Response Rate	79.4 Percentage of participants Interval 72.3 to 85.4	74.8 Percentage of participants Interval 67.4 to 81.4

SECONDARY outcome

Population: All participants in the randomised set with objective response.

Number of participants with objective response (best overall response of complete response or partial response) to study treatment over time, cumulative number of participants is displayed. Time to objective response was defined as the time from randomisation to the first recorded objective response. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.

Outcome measures

Outcome measures
Measure	Afatinib n=127 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=119 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Time to Objective Response Week 48	127 Participants	119 Participants
Time to Objective Response Week 4	81 Participants	74 Participants
Time to Objective Response Week 8	112 Participants	107 Participants
Time to Objective Response Week 16	119 Participants	117 Participants
Time to Objective Response Week 24	122 Participants	118 Participants
Time to Objective Response Week 32	125 Participants	118 Participants
Time to Objective Response Week 40	126 Participants	118 Participants

SECONDARY outcome

Population: Participants in the randomised set with objective response.

Duration of objective response defined as the time of first objective response (best overall response of complete response or partial response) to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.

Outcome measures

Outcome measures
Measure	Afatinib n=127 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=119 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Duration of Objective Response	11.86 Months Interval 10.12 to 15.54	11.07 Months Interval 9.69 to 12.91

SECONDARY outcome

Timeframe: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.

Population: Randomised set which included all patients randomised to receive treatment, whether treated or not.

Percentage of participants with disease control which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Responses of SD were only considered if they occur ≥42 days from date of randomisation. For the final analysis (analysis cut-off date 12 April 2019) disease control was determined by investigator assessment.

Outcome measures

Outcome measures
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=159 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Disease Control	94.4 Percentage of participants Interval 89.6 to 97.4	93.7 Percentage of participants Interval 88.7 to 96.9

SECONDARY outcome

Timeframe: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.

Population: All participants in the randomised set with disease control, that is, with best overall response of complete response or partial response or stable disease.

Duration of disease control defined as the time from randomisation to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) the status and date of disease progression were determined by investigator assessment.

Outcome measures

Outcome measures
Measure	Afatinib n=151 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=149 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Duration of Disease Control	12.88 Months Interval 11.14 to 14.88	11.73 Months Interval 10.58 to 14.55

SECONDARY outcome

Timeframe: From first drug administration until last drug administration, up to 1482 days

Population: Participants in the randomised set with tumour assessments.

Tumour shrinkage assessed by minimum sum of post-baseline target lesion diameters recorded after randomisation. A positive value shows a decrease in tumour size.

Outcome measures

Outcome measures
Measure	Afatinib n=149 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=151 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Tumour Shrinkage (Main Overall Survival Analysis Cut-off Date, 08 April 2016)	34.79 millimetre (mm) Interval 32.18 to 37.4	38.25 millimetre (mm) Interval 35.65 to 40.84

SECONDARY outcome

Timeframe: Every 8 weeks, up to 56 weeks

Population: All randomised subjects with health-related quality of life data.

Health-related quality of life (HRQoL) measured using European Quality of life - 5 Dimensions (EQ-5D) score for United Kingdom (UK) and Belgium and European European Quality Visual Analogue Scale (EQ-VAS). EQ-5D utility scores range from 0 (worst health) to 1 (full health). EQ-VAS scores range from 0 (worst imaginable health state) to 100 (best imaginable health state). Results display the mean score up to 56 weeks.

Outcome measures

Outcome measures
Measure	Afatinib n=160 Participants Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.	Gefitinib n=158 Participants Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015) EQ-5D UK utility score	0.77 Units on a scale Interval 0.75 to 0.8	0.80 Units on a scale Interval 0.77 to 0.82
Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015) EQ-5D Belgium utility score	0.74 Units on a scale Interval 0.72 to 0.77	0.77 Units on a scale Interval 0.75 to 0.8
Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015) EQ-VAS utility score	74.5 Units on a scale Interval 72.3 to 76.6	76.0 Units on a scale Interval 73.9 to 78.1

Adverse Events

Afatinib

Serious events: 75 serious events

Other events: 157 other events

Deaths: 126 deaths

Gefitinib

Serious events: 64 serious events

Other events: 159 other events

Deaths: 132 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

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.
Publication restrictions are in place

Restriction type: OTHER