In a phase I study, the PD-1 checkpoint inhibitor nivolumab administered in combination with platinum-based doublet chemotherapy (PT-DC) showed improved response rates but higher-than-expected occurrence of adverse events, investigators reported.

In the CheckMate 012 phase I, multicohort trial of nivolumab for first-line treatment of advanced non–small-cell lung cancer, treatment-related adverse events occurred in 95% of patients, and the overall response rates ranged from 33% to 47%.

“It is unclear at this time whether nivolumab plus PT-DC offers improved long-term [overall survival] benefit compared with nivolumab monotherapy,” wrote Naiyer Rizvi, MD, of Memorial Sloan-Kettering Cancer Center, New York, and his associates (J Clin Oncol. 2016 June. doi: 10.1200/JCO.2016.66.9861).

Fifty-six patients with newly-diagnosed advanced NSCLC were assigned by histology to receive one of four drug regimens: nivolumab at 10 mg/kg plus gemcitabine-cisplatin (squamous, n = 12), nivolumab at 10 mg/kg plus pemetrexed-cisplatin (nonsquamous, n = 15), nivolumab at 10mg/kg plus paclitaxel-carboplatin (any histology, n = 15), or nivolumab at 5 mg/kg plus paclitaxel-carboplatin (any histology, n = 14).

For all patients, nivolumab and PT-DC were administered intravenously on day 1 of each 21-day cycle for four cycles followed by nivolumab monotherapy every 3 weeks. Median follow-up time for safety and efficacy was 19.0 months.

No dose-limiting toxicities occurred in the first 6 weeks of treatment. In the overall population, 95% of patients experienced treatment-related adverse events, the most common being fatigue, nausea, and alopecia. Grade three or four adverse events occurred in 45% of patients. Specifically, among those treated with nivolumab at 10 mg/kg, 93% experienced any grade and 50% experienced grade 3 or 4 treatment-related adverse events. Adverse events led to the discontinuation of all study therapy in 21% of patients. No treatment-related deaths were reported.

Overall response was highest among patients receiving nivolumab plus pemetrexed-cisplatin or paclitaxel-carboplatin, both with rates of 47% (95% confidence interval, 21-73 for both treatment arms).

In addition, median progression-free survival ranged from 4.8 to 7.1 months across treatment arms and was longest among patients receiving nivolumab at 5 mg/kg in combination with paclitaxel-carboplatin.

Finally, there was no clear association between PD-L1 expression and outcome.

All 17 investigators reported serving in advisory roles for, receiving financial compensation or honoraria from, or having ownership or stock interest in multiple companies including Bristol-Myers Squibb, which funded the CheckMate 012 trial.

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