Phase 3
N=364
BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
Carcinoma, Non-Small-Cell Lung · Adenocarcinoma
Bottom Line
View on ClinicalTrials.gov: NCT01121393 ↗Enrolled (actual)
364
Serious AEs
14.8%
Results posted
Jan 2015
Primary outcome: Primary: Progression-free Survival — 11.01; 5.59 months — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Gemcitabine+Cisplatin (Drug); BIBW 2992 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival |
11.01; 5.59 | <0.0001 sig |
| SECONDARY Objective Response (OR) |
67.8; 23.0 | <0.0001 sig |
| SECONDARY Disease Control (DC) |
92.6; 76.2 | <0.0001 sig |
| SECONDARY Overall Survival (OS) |
23.10; 23.46 | 0.4013 |
| SECONDARY Time to Objective Response (OR) |
49.2; 13.1; 59.9; 19.7; 64.0; 23.0 | — |
| SECONDARY Duration of Objective Response |
9.72; 4.27 | — |
| SECONDARY Duration of Disease Control |
11.07; 5.65 | — |
| SECONDARY Tumour Shrinkage |
33.41; 47.06 | <0.0001 sig |
| SECONDARY Change From Baseline in Body Weight |
-3.03; -1.52; -0.76; 0.00 | — |
| SECONDARY Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) |
11.4; 21.8; 6.8; 3.6; 8.0; 14.5 | — |
| SECONDARY Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing |
31.05; 10.28 | 0.0001 sig |
| SECONDARY Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea |
7.66; 1.68 | <0.0001 sig |
| SECONDARY Health Related Quality of Life (HRQOL): Time of Deterioration in Pain |
6.93; 3.38 | 0.0220 sig |
| SECONDARY Pharmacokinetics of Afatinib at Day 22 |
17.7; 23.1 | — |
| SECONDARY Pharmacokinetics of Afatinib at Day 29 |
19.5; 23.8; 22.8 | — |
| SECONDARY Pharmacokinetics of Afatinib at Day 43 |
21.5; 22.1; 22.9 | — |
| SECONDARY Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events |
13.8; 8.0; 36.0; 29.2; 39.3; 38.1 | — |
| SECONDARY Changes in Safety Laboratory Parameters |
NA; NA; 5.1; 15.6; 2.6; 0.9 | — |
Summary
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
Eligibility Criteria
Inclusion criteria
- pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the Lung
- EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material
- Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST)1.1
- Eastern Cooperative Oncology Group (ECOG) 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 (ICH-GCP) guidelines.
Exclusion criteria
- Prior chemotherapy for relapsed and/or metastatic NSCLC.
- Prior treatment with EGFR targeting small molecules or antibodies.
- Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization
- Active brain metastases
- Any other current malignancy or malignancy diagnosed within the past 5 years
- Known pre-existing interstitial lung disease
- Significant or recent acute gastrointestinal disorders with diarrhoea as a a major symptoms.
- History or presence of clinically relevant cardiovascular abnormalities
- Cardiac left ventricular function with resting ejection fraction of less than 50%.
- Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
- Absolute neutrophil count(ANC) 1.5 times Upper Limit of Normal (ULN).
- Bilirubin>1.5 times ULN
- Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times ULN
- Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial
- Pregnancy of breast-feeding
- Patients unable to comply with the protocol
- Active hepatitis B infection, active hepatitis C infection or known HIV(Human Immunodeficiency Virus) carrier.
- Known or suspected active drug or alcohol abuse.
- requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2
- Any contraindications for therapy with gemcitabine/cisplatin
- Known hypersensitivity to BIBW2992 or the excipient of any of the trial drugs
- Use of any investigational drug within 4 weeks of randomization.
Data sourced from ClinicalTrials.gov (NCT01121393). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.