Pemetrexed plus platinum or gemcitabine plus platinum for advanced non‐small cell lung cancer: final survival analysis from a multicentre randomized phase II trial in the East Asia region and a meta‐analysis

Background and Objective: Pemetrexed plus platinum has shown efficacy as a first‐line treatment for advanced non–small cell lung cancer (NSCLC), but little is known about its efficacy and safety in East Asian patients. We report the final analysis of overall survival (OS) from a multicentre, randomized, phase II trial in chemotherapy‐naive Chinese patients with advanced NSCLC. An additional meta‐analysis was performed to systematically evaluate pemetrexed/platinum as first‐line treatment for advanced NSCLC. Methods: Eligible patients received up to six cycles of pemetrexed, 500 mg/m² plus cisplatin, 75 mg/m² (day 1) or gemcitabine, 1000 mg/m² (days 1 and 8) plus cisplatin, 75 mg/m² (day 1). OS and toxicity were assessed. Results: A total of 254 patients were randomized, and 251 were eligible for inclusion in the efficacy and safety analyses. Median OS in the pemetrexed/cisplatin arm was 15.3 months, compared with 16.9 months in the gemcitabine/cisplatin arm [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.80–1.48; log‐rank P = 0.4888). There was a trend towards improved survival in both arms. Patients in the pemetrexed/cisplatin arm showed a lower incidence of drug‐related grade 3 to 4 leukopenia and thrombocytopenia. Meta‐analysis showed that pemetrexed‐platinum treatment was associated with 19% longer survival among females (HR 0.81; 95% CI 0.69–0.96) and 17% longer survival among patients with non‐squamous cell lung cancer (HR 0.83; 95% CI 0.73–0.95). Conclusions: In Chinese patients with advanced NSCLC, pemetrexed/cisplatin treatment resulted in comparable OS outcomes and was better tolerated than gemcitabine/cisplatin. Meta‐analysis supports the use of pemetrexed‐platinum as first‐line treatment for female patients and those with the non‐squamous cell subtype of advanced NSCLC.