Nivolumab Combined with Platinum-Based Doublet Chemotherapy in Advanced NSCLC
Although platinum-based doublet chemotherapy (PBDC) has demonstrated 1-year overall survival (OS) rates of up to 54% in advanced non-small-cell lung cancer (NSCLC), there remains a need for therapies with improved long-term survival. The combination of chemotherapy with immunotherapy agents is of particular interest in light of their distinct mechanisms. Antonia and colleagues (ASCO 2014; Abstract 8113) reported an updated analysis of a phase 1 multicohort study evaluating the combination of nivolumab (NIV), a fully human PD-1 immune-checkpoint inhibitor antibody, and PBDC in chemotherapy-naïve patients with advanced NSCLC.
A total of 56 patients with advanced NSCLC were assigned based on histology to 4 cohorts to receive NIV (10 mg/kg every 3 weeks) plus concurrent gemcitabine (1250 mg/m2) + cisplatin (75 mg/m2) [squamous] or pemetrexed (500 mg/m2) + cisplatin (75 mg/m2) [nonsquamous], or NIV (5 or 10 mg/kg every 3 weeks) plus paclitaxel (200 mg/m2) + carboplatin (AUC6) [squamous and nonsquamous]. The PBDC regimens were given for 4 cycles and followed by NIV until progression or unacceptable toxicity. Objective response rate was assessed by RECIST 1.1.
No dose-limiting toxicities (DLTs) were observed during the first 6 weeks of treatment. Grade 3/4 treatment-related adverse events were reported in 45% of patients (25% to 73% across arms), including pneumonitis (4 patients, 7%; managed by protocol algorithm), fatigue, and acute renal failure (3 patients [5%] each). Across patient subgroups after more than 10 months of follow-up, overall response rate ranged from 33% to 50%. Progressive disease as best overall response was observed in only 3 of 56 patients. One-year OS rates ranged from 59% to 87% across histologic subgroups.
Antonia and colleagues concluded that NIV combined with standard PBDC regimens as first-line treatment for NSCLC exhibits antitumor activity with encouraging 1-year OS findings, and a tolerability profile reflecting additive toxicities of NIV and chemotherapy.