3-Year Follow-Up Data for Nivolumab Combined with Ipilimumab in Treatment-Naïve NSCLC: CheckMate-227
Researchers continue to explore the clinical efficacy of nivolumab combined with ipilimumab (NIVO + IPI) in treatment-naïve patients with advanced non–small-cell lung cancer (NSCLC). In Part 1 of the phase 3 CheckMate-227 study, first-line use of NIVO + IPI was shown to significantly improve overall survival (OS) compared with chemotherapy after a minimum follow-up of 29 months. At ASCO 2020, the CheckMate-227 researchers reported data after a minimum 3-year follow-up.
The CheckMate-227 trial has enrolled treatment-naïve patients with NSCLC, including patients whose tumor PD-L1 expression was ≥1% (for the primary analysis) or <1% (for the prespecified descriptive analysis). A total of 1189 patients with stage IV or recurrent NSCLC and PD-L1 expression ≥1% were randomized to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks), nivolumab alone (240 mg every 2 weeks), or chemotherapy. Among 550 patients whose PD-L1 expression level was <1%, randomized treatments included NIVO + IPI, nivolumab (360 mg every 3 weeks) plus chemotherapy, or chemotherapy.
In patients with PD-L1 expression ≥1%, the study’s primary end point was OS (NIVO + IPI vs chemotherapy). At 6 months, an exploratory analysis of OS in patients was conducted by patients’ response status: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Data were locked on February 28, 2020, after a median follow-up of 43.1 months. Among patients with PD-L1 expression ≥1%, continued OS benefit was observed with NIVO + IPI compared with chemotherapy (hazard ratio, 0.79; 95% confidence interval [CI], 0.67-0.93). The 3-year OS rates were 33% for NIVO + IPI, 29% for NIVO monotherapy, and 22% for chemotherapy. At 3 years, 18% of patients with PD-L1 levels ≥1% who were treated with NIVO + IPI remained progression-free compared with 12% of patients receiving NIVO and 4% of patients receiving chemotherapy. Among confirmed responders with PD-L1 levels ≥1%, 38% remained in response in the NIVO + IPI arm at 3 years compared with 32% in the NIVO arm and 4% in the chemotherapy arm.
In patients with PD-L1 levels <1%, the OS hazard ratio for NIVO + IPI compared with chemotherapy was 0.64 (95% CI, 0.51-0.81). The 3-year OS rates were 34% for NIVO + IPI, 20% for NIVO + chemotherapy, and 15% for chemotherapy. In this cohort, 13%, 8%, and 2% of patients remained progression-free after 3 years, respectively. In addition, 34%, 15%, and 0% of confirmed responders remained in response after 3 years, respectively.
Patients with PD-L1 expression ≥1% who achieved either CR or PR at 6 months had longer subsequent OS with NIVO + IPI compared with chemotherapy, while patients with SD or PD at 6 months had generally similar subsequent OS between treatments.
Treatment-related adverse events of any severity grade were observed in 77% of patients treated with NIVO + IPI and 82% of patients treated with chemotherapy. Severe (grade 3/4) treatment-related adverse events were observed in 33% of patients treated with NIVO + IPI and in 36% of patients undergoing chemotherapy.
Researchers concluded that, after a 3-year minimum follow-up, NIVO + IPI continued to provide durable and long-term OS benefit compared with chemotherapy in treatment-naïve patients with advanced NSCLC. Patients with PD-L1 expression levels ≥1% who achieved CR or PR at 6 months had marked OS benefit with NIVO + IPI relative to chemotherapy. No new safety signals were identified for NIVO + IPI. This dual immunotherapy regimen is a novel chemotherapy-sparing first-line treatment option for patients with advanced NSCLC.
Ramalingam SS, Ciuleanu TE, Pluzanski A, et al. Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: three-year update from CheckMate 227 Part 1. J Clin Oncol. 2020;38:suppl (abstract 9500).