Phase II Trial of BIBW 2992 in Suspected Mutant EGFR Lung Cancer Patients Unfit for Chemotherapy
Lung cancer is most common cause of death from cancer, of which non-small cell lung cancer
(NSCLC) accounts for ~80% of all cases with most patients presenting with advanced disease.
Patients medically unfit to receive radical or platinum-doublet palliative systemic therapy,
because of poor performance status or comorbidity, account for at least 45% of newly
diagnosed cases and have poor survival. Many oncologists have interpreted single-agent
chemotherapy data as not clinically meaningful when balanced against toxicities,
non-significant improvements in quality of life and comorbidity. Hence, in the UK, this
group of patients are predominantly treated by best-supportive care (BSC).
This study aims to examine the efficacy and safety of using an irreversible EGFR inhibitor
drug BIBW 2992 to treat patients with non-small cell lung cancer and suspected Epidermal
Growth Factor Receptor (EGFR) mutation who are considered unfit for chemotherapy. This drug
is currently unlicensed.
There has been only one small prospective study of medically unfit patients with EGFR
mutation, but it demonstrated good efficacy with a TKI17. This phase II study of East Asian
patients (n=30) with performance status 2-4 and treated with gefitinib demonstrated a rapid
improvement in performance status at 1 month, an overall response rate of 66% and median
survival of 17.8 months. Whilst gefitinib is licensed for EGFR mutant NSCLC, no prospective
studies have yet been performed on medically unfit patients from Western countries. Despite
dramatic initial responses, EGFR mutant NSCLC patients treated with gefitinib/erlotinib
ultimately relapse. In ~50% of cases this is due to the gefitinib/erlotinib-resistant T790M
genotype acquired through either secondary somatic mutation or clonal expansion. There is
therefore a need to improve the outcomes of medically unfit patients with suspected EGFR
mutation, who would otherwise be treated with best supportive care, and in proven EGFR
mutation cases by using an effective EGFR-directed therapy that inhibits EGFRT790M.
Prospective data on medically unfit Western NSCLC patients with EGFR mutation are required
to assess the efficacy of EGFR-TKIs. Additionally, given that 50% of such patients will
become TKI-resistant through EGFRT790M, new therapies are required to overcome this
We aim to recruit patients with clinical characteristics likely to harbour EGFR mutation but
with EGFR genotype unknown either due to no tissue suitable for genotyping, failed genotype;
these will be patients with adenocarcinoma who are never- or ex-light smokers.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression free survival
Progression free survival will be determined by measurement of tumour size using RECIST version 1.1 at progression or date of patient death.
At 6 months
Sanjay Popat, BSc MBBS MRCP PhD
Royal Marsden Hospital London
United Kingdom: Medicines and Healthcare Products Regulatory Agency