Among patients with completely resected non–small-cell lung cancer (NSCLC) whose tumors expressed epidermal growth factor receptor (EGFR), disease-free survival (DFS) rates were similar between erlotinib and placebo groups, according to results from the RADIANT phase III trial.
EGFR-activating mutations (EGFRm) were observed in a subgroup of patients (16.5%, 89 with del19 and 72 with L858R mutations) but these patients were not stratified by mutation status, which limited interpretation of the results. For the erlotinib vs. placebo arms of the EGFRm-positive subgroup, median DFS was 46.4 and 28.5 months, respectively, with 2-year DFS rates of 75% and 54%. The results were not statistically significant due to hierarchical testing. There were between-arm imbalances of disease characteristics, and the placebo arm of the EGFRm-positive subgroup had substantially worse DFS than the intention-to-treat population.
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“The trend toward improvement in DFS with erlotinib in the EGFRm-positive subgroup warrants further evaluation,” wrote Dr. Karen Kelly of UC Davis Comprehensive Cancer Center, Sacramento, California, and colleagues (J Clin Oncol. 2015 Aug 31. doi:10.1200/JCO.2015.61.8918).
The randomized, double-blind, placebo-controlled RADIANT trial included 973 patients with completely resected stage IB to IIIA NSCLC with EGFR-expressing tumors by immunohistochemistry (IHC) and EGFR high copy number or amplification by fluorescence in situ hybridization (FISH). Previous studies indicated that EGFR protein expression detected by IHC and FISH may be predictive of prolonged survival with EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib. However, subsequent to activation of the RADIANT trial, two phase III studies failed to show that IHC and FISH results were predictive of EGFR-TKI efficacy. Emerging data show that EGFRm-positive status is the strongest predictor of EFGR-TKI sensitivity.
The duration of treatment in the RADIANT trial was 2 years, but the authors speculate that, based on results from the recent SELECT trial in which only four patients experienced relapse while taking erlotinib, a longer treatment duration “may be needed to achieve the goal of increasing the cure rate of early-stage NSCLC in an EGFRm-positive population.”
KRAS mutation status, tested in 828 patient samples, was not prognostic and did not predict erlotinib benefit.
The study was supported by Astellas Pharma Global Development, F. Hoffmann-La Roche, and Genentech. Dr. Kelly reported having no disclosures. Several of her coauthors were employed by or reported consulting or advisory roles with industry sources.