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NCT01121393

BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)

Completed Phase 3 Results posted Last updated 14 December 2018
What this trial tests

Phase 3 trial testing Gemcitabine+Cisplatin in Carcinoma, Non-Small-Cell Lung in 364 participants. Completed in 26 November 2017.

Timeline
19 April 2010
Primary endpoint
23 November 2017
26 November 2017

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment364
Start date19 April 2010
Primary completion23 November 2017
Estimated completion26 November 2017
Sites36 locations across China, Thailand, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung or Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival Primary · 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

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.

GroupValue95% CI
Afatinib 40 Milligram (mg)11.019.66 – 13.73
Gemcitabine / Cisplatin Chemotherapy5.594.67 – 6.70
Objective Response (OR) Secondary · 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

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 Pea

GroupValue95% CI
Afatinib 40 Milligram (mg)67.861.5 – 73.6
Gemcitabine / Cisplatin Chemotherapy23.015.8 – 31.4
Disease Control (DC) Secondary · 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

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.

GroupValue95% CI
Afatinib 40 Milligram (mg)92.688.5 – 95.5
Gemcitabine / Cisplatin Chemotherapy76.267.7 – 83.5
Overall Survival (OS) Secondary · From randomisation up to 374 weeks

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.

GroupValue95% CI
Afatinib 40 Milligram (mg)23.1020.40 – 27.33
Gemcitabine / Cisplatin Chemotherapy23.4617.94 – 25.56
Time to Objective Response (OR) Secondary · 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

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.

By Week 6
GroupValue95% CI
Afatinib 40 Milligram (mg)49.2
Gemcitabine / Cisplatin Chemotherapy13.1
By Week 12
GroupValue95% CI
Afatinib 40 Milligram (mg)59.9
Gemcitabine / Cisplatin Chemotherapy19.7
By Week 18
GroupValue95% CI
Afatinib 40 Milligram (mg)64.0
Gemcitabine / Cisplatin Chemotherapy23.0
By Week 24
GroupValue95% CI
Afatinib 40 Milligram (mg)64.9
Gemcitabine / Cisplatin Chemotherapy23.0
By Week 30
GroupValue95% CI
Afatinib 40 Milligram (mg)65.7
Gemcitabine / Cisplatin Chemotherapy23.0
By Week 36
GroupValue95% CI
Afatinib 40 Milligram (mg)66.1
Gemcitabine / Cisplatin Chemotherapy23.0
By Week 42
GroupValue95% CI
Afatinib 40 Milligram (mg)66.5
Gemcitabine / Cisplatin Chemotherapy23.0
By Week 48
GroupValue95% CI
Afatinib 40 Milligram (mg)66.5
Gemcitabine / Cisplatin Chemotherapy23.0
Duration of Objective Response Secondary · 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

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.

GroupValue95% CI
Afatinib 40 Milligram (mg)9.728.34 – 12.45
Gemcitabine / Cisplatin Chemotherapy4.272.76 – 5.75
Duration of Disease Control Secondary · 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

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.

GroupValue95% CI
Afatinib 40 Milligram (mg)11.079.69 – 13.80
Gemcitabine / Cisplatin Chemotherapy5.655.49 – 6.93
Tumour Shrinkage Secondary · 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

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. T

GroupValue95% CI
Afatinib 40 Milligram (mg)33.41± 0.99
Gemcitabine / Cisplatin Chemotherapy47.06± 1.45
Change From Baseline in Body Weight Secondary · Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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

Change from baseline at lowest value
GroupValue95% CI
Afatinib 40 Milligram (mg)-3.03± 3.99
Gemcitabine / Cisplatin Chemotherapy-1.52± 3.65
Change from baseline at last value
GroupValue95% CI
Afatinib 40 Milligram (mg)-0.76± 4.79
Gemcitabine / Cisplatin Chemotherapy0.00± 4.52
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Secondary · Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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

ECOG PS 0 (baseline) 0 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)11.4
Gemcitabine / Cisplatin Chemotherapy21.8
ECOG PS 1 (baseline) 0 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)6.8
Gemcitabine / Cisplatin Chemotherapy3.6
ECOG PS 0 (baseline) 1 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)8.0
Gemcitabine / Cisplatin Chemotherapy14.5
ECOG PS 1 (baseline) 1 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)67.5
Gemcitabine / Cisplatin Chemotherapy51.8
ECOG PS 0 (baseline) 2 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)0.4
Gemcitabine / Cisplatin Chemotherapy0.0
ECOG PS 1 (baseline) 2 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)2.1
Gemcitabine / Cisplatin Chemotherapy1.8
ECOG PS 0 (baseline) 3 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)0.0
Gemcitabine / Cisplatin Chemotherapy0.0
ECOG PS 1 (baseline) 3 (last value)
GroupValue95% CI
Afatinib 40 Milligram (mg)2.1
Gemcitabine / Cisplatin Chemotherapy4.5
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing Secondary · Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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

GroupValue95% CI
Afatinib 40 Milligram (mg)31.0517.45 – NA
Gemcitabine / Cisplatin Chemotherapy10.284.63 – NA
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea Secondary · Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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 de

GroupValue95% CI
Afatinib 40 Milligram (mg)7.664.76 – 11.17
Gemcitabine / Cisplatin Chemotherapy1.681.38 – 3.15

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of study medication until 28 days after the last administration of study medication up to 374 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Afatinib 40 Milligram (mg)
Serious: 40/239 (17%)
Deaths: 16/239
Gemcitabine / Cisplatin Chemotherapy
Serious: 12/113 (11%)
Deaths: 3/113

Serious adverse events (61 terms)

ReactionSystemAfatinib 40 Milligram (mg)Gemcitabine / Cisplatin Ch…
Respiratory failureRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
PneumoniaInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
Vertigo positionalEar and labyrinth disorders
Abdominal distensionGastrointestinal disorders
ConstipationGastrointestinal disorders
DysphagiaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
DeathGeneral disorders
FatigueGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
PyrexiaGeneral disorders
Sudden deathGeneral disorders
Other adverse events (53 terms — click to expand)

ReactionSystemAfatinib 40 Milligram (mg)Gemcitabine / Cisplatin Ch…
DiarrhoeaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
ParonychiaInfections and infestations
NeutropeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Mouth ulcerationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
StomatitisGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
Weight decreasedInvestigations
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Neutrophil count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Chest painGeneral disorders
White blood cell count decreasedInvestigations
PruritusSkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
Haemoglobin decreasedInvestigations
DizzinessNervous system disorders
NasopharyngitisInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
Mucosal inflammationGeneral disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Skin fissuresSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Upper respiratory tract infectionInfections and infestations
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
InsomniaPsychiatric disorders

Most-reported serious reactions: Respiratory failure, Dyspnoea, Headache, Thrombocytopenia, Diarrhoea, Vomiting, Pneumonia, Decreased appetite.

Data from ClinicalTrials.gov NCT01121393 adverse events section.

Sponsor's own description

To investigate the efficacy and safety of BIBW 2992 compared to standard first-line chemotherapy in patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial.
    Wu YL, Zhou C, Hu CP, Feng J, et al · · 2014 · cited 1579× · PMID 24439929 · DOI 10.1016/s1470-2045(13)70604-1
  2. 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.
    Yang JC, Wu YL, Schuler M, Sebastian M, et al · · 2015 · cited 1201× · PMID 25589191 · DOI 10.1016/s1470-2045(14)71173-8
  3. 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.
    Yang JC, Sequist LV, Geater SL, Tsai CM, et al · · 2015 · cited 772× · PMID 26051236 · DOI 10.1016/s1470-2045(15)00026-1
  4. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09).
    Cho JH, Lim SH, An HJ, Kim KH, et al · · 2020 · cited 271× · PMID 31825714 · DOI 10.1200/jco.19.00931
  5. Targeting <i>EGFR</i> exon 20 insertion mutations in non-small cell lung cancer.
    Vyse S, Huang PH. · · 2019 · cited 262× · PMID 30854234 · DOI 10.1038/s41392-019-0038-9
  6. Current Landscape of Non-Small Cell Lung Cancer: Epidemiology, Histological Classification, Targeted Therapies, and Immunotherapy.
    Rodak O, Peris-Díaz MD, Olbromski M, Podhorska-Okołów M, et al · · 2021 · cited 159× · PMID 34572931 · DOI 10.3390/cancers13184705
  7. Clinical development of targeted and immune based anti-cancer therapies.
    Seebacher NA, Stacy AE, Porter GM, Merlot AM. · · 2019 · cited 147× · PMID 30975211 · DOI 10.1186/s13046-019-1094-2
  8. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer.
    Hirsh V. · · 2011 · cited 98× · PMID 21655159 · DOI 10.3747/co.v18i3.877

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