(ChemotherapyAdvisor) – The TORCH trial has found sequencing of erlotinib affects overall survival in patients with advanced non-small cell lung cancer (NSCLC), with first-line erlotinib followed at disease progression by cisplatin-gemcitabine to be significantly inferior than the standard inverse sequence, results reported in the Journal of Clinical Oncology July 9 has found.
“To the best of our knowledge, TORCH is the first trial testing the hypothesis that single-agent erlotinib might be an alternative to first-line chemotherapy in unselected patients with advanced NSCLC,” the investigators reported. However, “at the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study.”
A total of 760 patients with stage IIIB/IV NSCLC were randomly assigned to the standard arm, of which 97.6% received at least one cycle of first-line cisplatin plus gemcitabine, or the experimental arm, of which 98.2% received at least one dose of first-line erlotinib. Median age was 62 years (range, 27-81 years).
Median follow-up as of June 1, 2011 was 24.3 months, with 536 deaths recorded, 263 in the standard treatment arm and 273 in the experimental arm. Median survival was 11.6 months (95% CI, 10.2–13.3) in the standard arm compared with 8.7 months (95% CI, 7.4–10.5) in the experimental arm. Adjusted HR of death was 1.24 (95% CI, 1.04–1.47) in the experimental arm. No heterogeneity was observed across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation.
“Given the critical role played by EGFR mutations in predicting efficacy of TKIs, the negative result of TORCH in a Western unselected population is consistent with the prevalence of such mutations that is substantially lower than that in East Asian patients: the proportion of patients with EGFR mutations was 16.6% in a series of 2,105 Western patients with nonsquamous cancer,” they noted. “TORCH data (with only 3% of East Asian patients) confirm this low prevalence (14.2%).”