A joint analysis of parallel phase III trials reported in the Journal of Clinical Oncology by Gridelli et al found no overall survival benefit of adding cisplatin to first-line treatment of elderly patients with advanced non–small cell lung cancer (NSCLC) without an EGFR mutation.
The combined analysis included two trials (MILES-3 and MILES-4) evaluating the addition of cisplatin to single-agent treatment in untreated advanced NSCLC with any (MILES-3) or nonsquamous (MILES-4) histology. The trials were closed early due to slow accrual, but the joint database permitted analysis of the efficacy of adding cisplatin on the basis of intention-to-treat with adjustment for trial, histotype, nonplatinum companion drug, stage, performance status, sex, and age.
For purposes of the current analysis, 531 patients (MILES-3 = 299, MILES-4 = 232) were randomized between March 2011 and August 2016 to receive gemcitabine or pemetrexed with (n = 263) or without (n = 268) cisplatin. Patients had a median age of 75 years, 79% were male, and 70% had nonsquamous histology.
Median follow-up was 2 years. Median overall survival was 9.6 months with combination treatment vs 7.5 months with single-agent treatment (hazard ratio [HR] = 0.86, P = .14). Quality of life assessed with the EORTC QLQ-C30 (transformed to a 100-point scale) showed no difference between groups; improvements of ≥ 10 points were observed in 37% vs 39% of patients (P = .80). Median progression-free survival was 4.6 months in the combination group vs 3.0 months in the monotherapy group (HR = 0.76, P = .005). Objective response rates were 15.5% vs 8.5% (P = .02).
Patients in the cisplatin group had significantly more hematologic and neurologic toxicity, mucositis, nausea, and vomiting, as well as significantly more severe thrombocytopenia, leukopenia, neutropenia, febrile neutropenia, fatigue, and anorexia.
The investigators concluded, “The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.”
The study was supported by a grant from the Italian Drug Agency and by Eli Lilly.
Cesare Gridelli, MD, of the Azienda Ospedaliera San Giuseppe Moscati, Avellino, is the corresponding author of the Journal of Clinical Oncology article.
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