The purpose of this study is to examine the efficacy and safety of using afatinib (BIBW 2992) to treat non-small cell lung cancer patients considered unfit for chemotherapy and have either suspected or confirmed Epidermal Growth Factor Receptor (EGFR) mutation.
Name: Afatinib (BIBW 2992)
Description: Progression free survival will be determined by measurement of tumour size using RECIST version 1.1 at progression or date of patient death.
Measure: Progression free survival Time: At 6 monthsDescription: For each type of adverse event, the maximum toxicity grade will be obtained for each patient using CTCAE version 4.0 to closely monitor tolerability to BIBW 2992. Focus will be on those with a grade 3 or 4 BIBW 2992 related toxicities. The proportion of patients with any grade 3 or 4 event will also be examined.
Measure: Safety Time: To be assessed at every timepoint i.e. baseline, fortnightly for the first 2 cycles and then monthly for 12 months and 2 monthly thereafterAllocation: N/A
Single Group Assignment
There are 2 SNPs
L858R, exon 19 deletions, exon 20 insertions, T790M, list is not exhaustive), and WHO PS 0-3 Or No tissue suitable for EGFR genotyping, failed genotype, or EGFR genotyping unavailable, and NSCLC Adenocarcinoma sub-type, and Eligible smoking history: Never smoker (<100 cigarettes in lifetime), or Former smoker (stopped >1year ago and ≤10 pack-years) and WHO PS 0-2 - Unsuitable for or patient declining chemotherapy due to significant co-morbidity - Measurable disease according to RECIST version 1.1 - Adequate haematopoietic, hepatic and renal function defined as follows: Absolute neutrophil count (ANC) ≤1.5 x 109/L and platelet count ≤100 x 109/L - Bilirubin ≤1.5 x ULN, ALT (SGPT) ≤3 x ULN (or ≤ 5 x ULN in cases of liver metastases) - Serum creatinine clearance ≥45 ml/min - Palliative radiotherapy allowed unless to a solitary target lesion - Age 18 or over (no upper age limit) - Written informed consent that is consistent with ICH-GCP guidelines Exclusion Criteria: - Previous treatment with afatinib (BIBW 2992), or any EGFR-directed inhibitor - Any concurrent anticancer systemic therapy - 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 registration - Suitable for radical radiotherapy - Palliative radiotherapy within 2 weeks prior to registration - Palliative radiotherapy to a solitary target lesion - Surgery (other than biopsy) within 4 weeks prior to registration - Inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption, any medical co- morbidity affecting gastrointestinal absorption - Patients with current or pre-existing interstitial lung disease - Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's participation in the trial - Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE version 4.0 Grade ≥3 diarrhoea of any etiology at baseline - Active brain metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants and/or leptomeningeal disease). --- L858R ---
L858R, exon 19 deletions, exon 20 insertions, T790M, list is not exhaustive), and WHO PS 0-3 Or No tissue suitable for EGFR genotyping, failed genotype, or EGFR genotyping unavailable, and NSCLC Adenocarcinoma sub-type, and Eligible smoking history: Never smoker (<100 cigarettes in lifetime), or Former smoker (stopped >1year ago and ≤10 pack-years) and WHO PS 0-2 - Unsuitable for or patient declining chemotherapy due to significant co-morbidity - Measurable disease according to RECIST version 1.1 - Adequate haematopoietic, hepatic and renal function defined as follows: Absolute neutrophil count (ANC) ≤1.5 x 109/L and platelet count ≤100 x 109/L - Bilirubin ≤1.5 x ULN, ALT (SGPT) ≤3 x ULN (or ≤ 5 x ULN in cases of liver metastases) - Serum creatinine clearance ≥45 ml/min - Palliative radiotherapy allowed unless to a solitary target lesion - Age 18 or over (no upper age limit) - Written informed consent that is consistent with ICH-GCP guidelines Exclusion Criteria: - Previous treatment with afatinib (BIBW 2992), or any EGFR-directed inhibitor - Any concurrent anticancer systemic therapy - 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 registration - Suitable for radical radiotherapy - Palliative radiotherapy within 2 weeks prior to registration - Palliative radiotherapy to a solitary target lesion - Surgery (other than biopsy) within 4 weeks prior to registration - Inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption, any medical co- morbidity affecting gastrointestinal absorption - Patients with current or pre-existing interstitial lung disease - Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's participation in the trial - Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE version 4.0 Grade ≥3 diarrhoea of any etiology at baseline - Active brain metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants and/or leptomeningeal disease). --- L858R --- --- T790M ---
In ~50% of cases this is due to the gefitinib/erlotinib-resistant T790M genotype acquired through either secondary somatic mutation or clonal expansion. --- T790M ---