Four-Year Update from CheckMate-227 Study of Nivolumab plus Ipilimumab in Advanced NSCLC
After 4 years of follow-up, nivolumab combined with ipilimumab provides durable, long-term survival benefit compared with chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) regardless of PD-L1 expression.
The combination of nivolumab (NIVO) and ipilimumab (IPI) was shown to provide durable long-term overall survival (OS) benefit compared with chemotherapy regardless of tumor PD-L1 expression in patients with advanced non–small-cell lung cancer (NSCLC) in CheckMate-227 Part 1. In this study, the 3-year OS rates were 33% compared with 22% in patients with PD-L1 expression levels of ≥1% (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67-0.93).1 Three-year OS rates were 34% compared with 15% in patients with PD-L1 expression levels <1% (HR, 0.64; 95% CI, 0.51-0.81).1 At the American Society of Clinical Oncology 2021 annual meeting, researchers reported updated results from the CheckMate-227 study with 4 years’ minimum follow-up.1
Adults with previously untreated stage IV or recurrent NSCLC, no known EGFR or ALK alterations, and Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled in CheckMate-227. Patients were stratified by histology: squamous and nonsquamous. A total of 1189 patients with PD-L1 ≥1% were randomized to receive NIVO at a dose of 3 mg/kg every 2 weeks plus IPI at a dose of 1 mg/kg every 6 weeks, NIVO alone (240 mg every 2 weeks), or chemotherapy. Another 550 patients with PD-L1 <1% were randomized to receive NIVO + IPI, NIVO (360 mg every 3 weeks) + chemotherapy, or chemotherapy alone. The primary end point was OS with NIVO + IPI compared with chemotherapy in patients with PD-L1 ≥1%.1
After minimum follow-up of 49.4 months (database lock, February 18, 2021), patients were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Patients with PD-L1 ≥1% continued to show a durable OS benefit with NIVO + IPI compared with chemotherapy (HR, 0.76; 95% CI, 0.65-0.90).1 Four-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemotherapy).1 At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemotherapy) remained progression-free.1 Among responders, 34%, 30%, and 7% remained in response, respectively.1
In an exploratory analysis in patients with PD-L1 ≥50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemotherapy).1 In patients with PD-L1 <1%, OS HR for NIVO + IPI versus chemotherapy was 0.64 (95% CI, 0.51-0.81) and 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemotherapy), and 10% (chemotherapy).1 At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemotherapy), and 0% (chemotherapy) remained progression-free.1 Among responders, 31%, 13%, and 0% remained in response, respectively.1
Among patients who progressed on NIVO + IPI versus chemotherapy, 7% versus 40% (PD-L1 ≥1%), and 9% versus 33% (PD-L1 <1%), received subsequent immunotherapy.1 Benefit with NIVO + IPI compared with chemotherapy was observed regardless of NSCLC histology.1 With long-term follow-up, no new safety signals were identified.1
Researchers concluded that after 4 years’ minimum follow-up, first-line NIVO + IPI continued to provide durable, long-term OS benefit compared with chemotherapy in patients with advanced NSCLC regardless of PD-L1 expression or histology.1Reference
1. Paz-Ares LG, Ciuleanu T-E, Lee J-S, et al. Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227. Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9016.