Trial Outcomes & Findings for LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment (NCT NCT01125566)

Last Updated: 2019-07-18

Results Overview

PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered. Progression of disease was determined if at least 1 of the following criteria applied: * At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm * Appearance of 1 or more new lesions * Unequivocal progression of existing non-target lesions

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

508 participants

Primary outcome timeframe

From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months

Results posted on

2019-07-18

Participant Flow

This was randomised, active-controlled, open-label, parallel-group, 2 arm (2:1 ratio) trial in participants with metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer failing one prior trastuzumab treatment.

Participants were treated in the study until disease progression, undue toxicity, or withdrawal of consent. The cut-off date for RECIST-based efficacy was 08 Jun 2013; a second analysis (primarily for assessing Overall Survival (OS)) contains all data until final database lock (30 Jul 2018).

Participant milestones

Participant milestones
Measure	Afatinib + Vinorelbine (AV) Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.	AV Switched to TV This group describes participants who discontinued AV treatment and switched to TV, provided they were without disease progression on AV, following data monitoring committee (DMC) recommendation to terminate recruitment on 26 April 2013.
Patients Before the Switch (26Apr2013) STARTED	339	169	0
Patients Before the Switch (26Apr2013) Treated	337	169	0
Patients Before the Switch (26Apr2013) COMPLETED	74	0	0
Patients Before the Switch (26Apr2013) NOT COMPLETED	265	169	0
Patients Who Switched From AV to TV STARTED	0	0	75
Patients Who Switched From AV to TV COMPLETED	0	0	2
Patients Who Switched From AV to TV NOT COMPLETED	0	0	73

Reasons for withdrawal

Reasons for withdrawal
Measure	Afatinib + Vinorelbine (AV) Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.	AV Switched to TV This group describes participants who discontinued AV treatment and switched to TV, provided they were without disease progression on AV, following data monitoring committee (DMC) recommendation to terminate recruitment on 26 April 2013.
Patients Before the Switch (26Apr2013) Progressive disease according to RECIST	182	119	0
Patients Before the Switch (26Apr2013) Worsening of underlying cancer disease	6	6	0
Patients Before the Switch (26Apr2013) Adverse Event	25	5	0
Patients Before the Switch (26Apr2013) Protocol Violation	0	2	0
Patients Before the Switch (26Apr2013) Refused to continue taking medication	24	23	0
Patients Before the Switch (26Apr2013) Not treated	2	0	0
Patients Before the Switch (26Apr2013) Other than listed above	25	13	0
Patients Before the Switch (26Apr2013) Lost to Follow-up	1	1	0
Patients Who Switched From AV to TV Progressive disease according to RECIST	0	0	59
Patients Who Switched From AV to TV Refused to continue taking medication	0	0	7
Patients Who Switched From AV to TV Worsening of underlying cancer disease	0	0	3
Patients Who Switched From AV to TV Other than listed above	0	0	4

Baseline Characteristics

Ethnicity data was not reported for this trial.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Afatinib + Vinorelbine (AV) n=332 Participants Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) n=168 Participants Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.	Total n=500 Participants Total of all reporting groups
Age, Continuous	51.8 Years STANDARD_DEVIATION 11.3 • n=332 Participants	53.1 Years STANDARD_DEVIATION 12.3 • n=168 Participants	52.2 Years STANDARD_DEVIATION 11.6 • n=500 Participants
Sex: Female, Male Female	332 Participants n=332 Participants	168 Participants n=168 Participants	500 Participants n=500 Participants
Sex: Female, Male Male	0 Participants n=332 Participants	0 Participants n=168 Participants	0 Participants n=500 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	—	—	0 Participants Ethnicity data was not reported for this trial.
Ethnicity (NIH/OMB) Not Hispanic or Latino	—	—	0 Participants Ethnicity data was not reported for this trial.
Ethnicity (NIH/OMB) Unknown or Not Reported	—	—	0 Participants Ethnicity data was not reported for this trial.
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=332 Participants	1 Participants n=168 Participants	2 Participants n=500 Participants
Race (NIH/OMB) Asian	172 Participants n=332 Participants	81 Participants n=168 Participants	253 Participants n=500 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=332 Participants	0 Participants n=168 Participants	0 Participants n=500 Participants
Race (NIH/OMB) Black or African American	6 Participants n=332 Participants	3 Participants n=168 Participants	9 Participants n=500 Participants
Race (NIH/OMB) White	136 Participants n=332 Participants	72 Participants n=168 Participants	208 Participants n=500 Participants
Race (NIH/OMB) More than one race	0 Participants n=332 Participants	0 Participants n=168 Participants	0 Participants n=500 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=332 Participants	11 Participants n=168 Participants	28 Participants n=500 Participants

PRIMARY outcome

Timeframe: From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months

Population: Randomised set (RS): The randomised set included all participants who were randomised to receive treatment, whether treated or not.

Outcome measures

Outcome measures
Measure	Afatinib + Vinorelbine (AV) n=339 Participants Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) n=169 Participants Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.
Progression-free Survival (PFS)	5.49 Months Interval 3.55 to 9.07	5.55 Months Interval 3.55 to 10.84

SECONDARY outcome

Timeframe: From randomisation (07Sep2010) to database lock (30Jul2018), up to 95 months.

Population: RS including participants with available data for OS.

OS is defined as time from randomisation to death irrespective of the cause of the death. For patients who had not died up to the cut-off date (03Sep2013), the date they were last known to be alive was derived from the patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.

Outcome measures

Outcome measures
Measure	Afatinib + Vinorelbine (AV) n=339 Participants Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) n=169 Participants Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.
Overall Survival (OS)	20.17 Months Interval 10.74 to 39.52	29.60 Months Interval 13.34 to 43.99

SECONDARY outcome

Timeframe: From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months

Population: RS including participants with available data for best RECIST assessment.

Best RECIST assessment is defined as CR, PR, stable disease (SD), progressive disease (PD) or not evaluable by investigator (RECIST version 1.1). CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis). PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study. PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Afatinib + Vinorelbine (AV) n=334 Participants Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) n=168 Participants Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.
Best RECIST Assessment Complete response (CR)	3.3 Percentage of participants	3.0 Percentage of participants
Best RECIST Assessment Partial response (PR)	43.1 Percentage of participants	44.0 Percentage of participants
Best RECIST Assessment Stable disease (SD)	31.7 Percentage of participants	26.8 Percentage of participants
Best RECIST Assessment Progressive Disease (PD)	12.6 Percentage of participants	17.9 Percentage of participants
Best RECIST Assessment Missing	9.3 Percentage of participants	8.3 Percentage of participants

SECONDARY outcome

Timeframe: Post baseline tumour-imaging was performed at Week 8, 16, 24, 32, 40, 48, 56 and then every 12 weeks (Until final data-base lock on 30 Jul 2018; Up to 95 months)

Population: RS including participants with available data for OR.

OR is defined as complete response (CR) and partial response (PR). Assessed by investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. Complete Response (CR) for target lesions (TL): Disappearance of all target lesions. Complete Response (CR) for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis) Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Other factors which add to the overall response of an imaging timepoint as PR are as below:- * CR in TL, but non-CR/Non-PD in NTL leads to PR * CR in TL, but not evaluated NTL leads to PR * PR in TL, but non-PD NTL or not all evaluated NTL leads to PR

Outcome measures

Outcome measures
Measure	Afatinib + Vinorelbine (AV) n=334 Participants Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter\^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	Trastuzumab + Vinorelbine (TV) n=168 Participants Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m\^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.
Objective Response (OR)	46.4 Percentage of participants (%) Interval 0.41 to 0.519	47.0 Percentage of participants (%) Interval 0.393 to 0.549

Adverse Events

Afatinib + Vinorelbine (AV)

Serious events: 123 serious events

Other events: 331 other events

Deaths: 235 deaths

Trastuzumab + Vinorelbine (TV)

Serious events: 45 serious events

Other events: 163 other events

Deaths: 111 deaths

AV Switched to TV

Serious events: 15 serious events

Other events: 64 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

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.\>
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