CheckMate-227: Nivolumab plus Ipilimumab in Advanced NSCLC – Four-Year Update

Nivolumab/ipilimumab (NIVO/IPI) combination therapy in patients with advanced non–small-cell lung cancer (NSCLC) in CheckMate-227 part 1 provided durable long-term overall survival (OS) benefit compared with chemotherapy independent of tumor PD-L1 expression. The 3-year OS rates were 33%/34% for the NIVO/IPI arm versus 22%/15% for the chemotherapy arm in patients with PD-L1 expression levels of ≥1% (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67-0.93) and PD-L1 expression levels of <1% (HR, 0.64; 95% CI, 0.51-0.81), respectively.¹ Researchers presented updated results from CheckMate-227 with ≥4 years of follow-up at ASCO 2021.¹

CheckMate-227 enrolled adults with previously untreated stage IV or recurrent NSCLC, no sensitizing EGFR mutations or known ALK alterations, and Eastern Cooperative Oncology Group performance status of 0 or 1 and stratified patients by histology: squamous and nonsquamous. After randomization (n = 1189), patients with PD-L1 ≥1% received NIVO 3 mg/kg every 2 weeks plus IPI 1 mg/kg every 6 weeks, NIVO alone (240 mg every 2 weeks), or chemotherapy. An additional 550 patients with PD-L1 <1% were randomized to receive NIVO/IPI, NIVO (360 mg every 3 weeks) plus chemotherapy, or chemotherapy alone. A primary end point was OS for patients with PD-L1 ≥1% in the NIVO/IPI arm compared with chemotherapy alone.¹

After a follow-up of ≥49.4 months, patients were ≥2 years beyond the protocol-specified end of immunotherapy treatment, and patients with PD-L1 ≥1% continued to demonstrate a durable OS benefit from 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), and, at 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemotherapy) remained progression-free.¹ Among responders, 34%, 30%, and 7% maintained a response, respectively.¹

In patients with PD-L1 ≥50%, 4-year OS rates were 37% (NIVO/IPI), 26% (NIVO), and 20% (chemotherapy) in an exploratory analysis.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 + chemo), and 10% (chemotherapy).¹ At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression-free.¹ Among patients with PD-L1 <1%, 31%, 13%, and 0% remained in response, respectively.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

After ≥4 years of follow-up in patients with advanced NSCLC, first-line NIVO/IPI continued to provide durable, long-term OS benefit compared with chemotherapy regardless of PD-L1 expression or histology.¹

Reference

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. American Society of Clinical Oncology (ASCO), June 2021; Abstract 9016.