Nivolumab (Opdivo) was found to be active combined with platinum-based doublets as first-line treatment of advanced non–small cell lung cancer (NSCLC), as part of the phase I CheckMate 012 study reported by Rizvi et al in the Journal of Clinical Oncology. The study is also evaluating nivolumab monotherapy in this setting.
A total of 56 patients with stage IIIB or IV disease received nivolumab plus a platinum-based doublet every 3 weeks for 4 cycles followed by nivolumab alone until disease progression or unacceptable toxicity. Treatments consisted of nivolumab at 10 mg/kg plus gemcitabine/cisplatin (n = 12; for squamous histology) or pemetrexed (Alimta)/cisplatin (n = 15; nonsquamous histology) or nivolumab at 5 (n = 14) or 10 mg/kg (n = 15) plus paclitaxel/carboplatin (all histologies).
No dose-limiting toxicities were observed during the first 6 weeks of treatment. Grade 3 or 4 treatment-related adverse events occurred in 45% of patients, with the most common being pneumonitis (7%) and acute renal failure (5%). Treatment-related adverse events led to discontinuation of all study therapy in 21% of patients.
Objective response rates were 33%, 47%, 47%, and 43% with nivolumab at 10 mg/kg plus gemcitabine/cisplatin, nivolumab at 10 mg/kg plus pemetrexed/cisplatin, nivolumab at 10 mg/kg plus paclitaxel/carboplatin, and nivolumab at 5 mg/kg plus paclitaxel/carboplatin, respectively. Median durations of response were 10.3, 5.8, 5.5, and 19.6 months. Progression-free survival at 24 weeks was 51%, 71%, 38%, and 51%. Two-year overall survival was 25%, 33%, 27%, and 62%. Responses were observed irrespective of tumor PD-L1 (programmed cell death ligand 1) expression status.
The investigators concluded: “The safety profile of nivolumab plus [platinum-base doublet chemotherapy] was consistent with that expected for individual agents; however, treatment discontinuation related to [adverse events] was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year [overall survival] rate of 62%.”
The study was supported by Bristol-Myers Squibb.
Naiyer A. Rizvi, MD, of Columbia University Medical Center, is the corresponding author of the Journal of Clinical Oncology article.