Efficacy and Safety Study of Afatinib to Treat Lung Cancer Patients — TIMELY  

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title: Trial of Afatinib (BIBW 2992) in Suspected or Confirmed Mutant EGFR Lung Cancer Patients Unfit for Chemotherapy

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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 afatinib (BIBW 2992), an irreversible second generation EGFR inhibitor, in patients with non-small cell lung cancer, who are considered unfit for chemotherapy and have either suspected or confirmed Epidermal Growth Factor Receptor (EGFR) mutation.

Suspected EGFR mutant patients will have clinical characteristics likely to harbour the EGFR mutation (adenocarcinoma sub type and ex or never smokers) with EGFR genotype unknown either due to no tissue suitable for genotyping or failed genotype.

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 resistance mechanism. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

• NCT number: NCT01415011
• Study type: Interventional
• Source: University College, London
• Status: Completed
• Phase: Phase 2
• Start date: December 2012
• Completion date: November 30, 2018