Efficacy of platinum-based doublet chemotherapy has plateaued, with objective response rates (ORR) of 25% to 35%, and 1- and 2-year survival rates from 30% to 40% and 10% to 15%, respectively.a Nivolumab (NIVO), a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has demonstrated durable responses and tolerability in heavily pretreated patients with advanced NSCLC.b Gettinger and colleaguesc now reported results from a phase 1 study that evaluated the efficacy and safety of NIVO monotherapy in patients with chemotherapy-naïve stage IIIB/IV NSCLC. A total of 52 patients with squamous (SQ) or non-SQ advanced NSCLC received NIVO 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. Response by RECIST v1.1 was evaluated overall, by histology, and by tumor PD-L1 expression (PD-L1 positivity was assigned to tumors where ?5% tumor cells expressed PD-L1).
After a minimum follow-up of 62.2 weeks, the objective response rate (ORR) was 23%, with 4 confirmed complete responses; 9/11 responders (82%) achieved response by the first CT scan (week 11). Median duration of response (mDOR) was not reached (NR; range, 18.1- 112.3+ weeks); 9 patients (82%) had ongoing responses at last tumor assessment. Median overall survival (mOS) was 22.6 months (range, 0.2-30.1+). Objective responses were observed in both PD-L1(+) and PD-L1(–) patients, with ORR higher in patients with PD-L1(+) tumors. In patients with non-SQ NSCLC, responses were noted regardless of EGFR or KRAS mutation status, but ORR and disease-free survival were higher among patients with a history of smoking. Most treatment-related adverse events were low grade, with the most common being rash, increased amylase/lipase, elevated liver function enzymes, hyperglycemia, cardiac failure, lung infection, and pneumonitis. The authors concluded that this study shows that first-line NIVO monotherapy resulted in durable responses, encouraging overall survival, and a tolerable safety profile in patients with advanced NSCLC. Although the response rates were higher in PD-L1(+) patients, OS was encouraging in both PD-L1(+)and PD-L1(–) patients. A phase 3 trial is underway to evaluate NIVO monotherapy versus investigator’s choice of chemotherapy in stage IV or recurrent PD-L1(+) NSCLC.
