Frontline Nivolumab Plus Ipilimumab Show Long-Term Benefit in mNSCLC

Luis Paz-Ares, MD, PhD

After 4 years of treatment with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), the therapy showed durable, long-term overall survival (OS) benefit compared with chemotherapy in patients with advanced non‒small cell lung cancer (NSCLC) regardless of PD-L1 expression or histology, according to a presentation at the 2021 ASCO Annual Meeting.¹

Progression-free survival (PFS) and duration of response (DOR) benefits were also maintained at 4 years, said lead author Luis Paz-Ares, MD, PhD, head of the H12O-CNIO Lung Cancer Clinical Research Unit of the Spanish National Cancer Research Centre (CNIO), in Madrid, Spain.

“Taken together, these updated results continue to support the use of nivolumab/ipilimumab as a first-line treatment of advanced NSCLC,” he said.

Paz-Ares presented updated 4-year efficacy and safety results for Part 1 of CheckMate-227 (NCT02477826) and a post-hoc efficacy analysis in patients who discontinued the nivolumab/ipilimumab combination because of treatment-related adverse events (TRAEs). The database was locked in February 2021 at a median follow up 54.8 months.

The median 4-year OS in patients with PD-L1 greater than or equal to 50% who received nivolumab/ipilimumab was 21.2 months (95% CI, 15.5-31.6). The hazard ratio (HR) compared with chemotherapy was 0.66 (95% CI, 0.52-0.84). For patients receiving nivolumab alone, the median OS was 18.1 months (95% CI, 14.4-22.1) with an HR of 0.64 (95% CI, 0.51-0.81) compared with chemotherapy. For patients receiving chemotherapy, the OS was 14.0 months (95% CI, 10.0-18.6).

Median 4-year OS in patients with PD-L1 less than 1% who received nivolumab/ipilimumab was 17.2 months (HR, 0.64; 95% CI, 0.51-0.81). For patients receiving nivolumab plus chemotherapy, the OS was 15.2 months (95% CI, 12.3-19.8). For patients receiving chemotherapy, the OS was 12.2 months (95% CI, 9.2-14.3)

Four-year updated DOR in patients with PD-L1 greater than or equal to 1% who received nivolumab/ipilimumab was 23.2 months (95% CI, 15.5-33.9). The DOR for patients with PD-L1 ≥ 1% who received nivolumab alone was 15.5 months (95% CI, 12.7-20.8). DOR was 6.7 months (95% CI, 5.6-7.6) for patients who received chemotherapy.

For patients with PD-L1 ≥ 50%, the 4-year updated DOR in patients who received nivolumab/ipilimumab was 31.8 months (95% CI, 20.7-51.2). For those who received nivolumab alone, the DOR was 16.8 months (95% CI, 13.5-29.6). DOR was 5.8 months (95% CI, 4.5-6.9) for patients receiving chemotherapy.

Four-year updated DOR in patients with PD-L1 < 1% who received nivolumab/ipilimumab was 18.0 months (95% CI, 12.4-33.2) compared with 8.3 months (95% CI, 5.9-9.4) for those who received nivolumab plus chemotherapy. For patients receiving chemotherapy only, the DOR was 4.8 months (95% CI, 3.7-5.8).

Sixty-six patients (17%) with PD-L1 ≥ 1 discontinued nivolumab/ipilimumab because of TRAEs. The median DOR after discontinuation was 52.6 months. Ninety-seven patients with PD-L1 ≥ 1% and < 1% discontinued nivolumab/ipilimumab because of TRAEs. The median DOR after discontinuation was 34.2 months in this group.

“In a post-hoc analysis, discontinuation of nivolumab/ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients,” Paz-Ares said. “Approximately half of the responders who had a TRAE leading to discontinuation maintained their responses for at least 3 years after treatment discontinuation.”

The FDA approved the combination of nivolumab/ipilimumab in May 2020 as a first-line treatment for patients with metastatic NSCLC with PD-L1 ≥ 1% based on the CheckMate-227 study (NCT02477826). The most common (20% or more) adverse reactions in patients receiving the combination were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritis, nausea, and hepatitis.²

The agency also approved the combination of nivolumab/ipilimumab plus chemotherapy in May 2020 as a first-line treatment for patients with metastatic NSCLC. This based on the CheckMate-9LA study (NCT03215706). OS for patients treated with nivolumab plus ipilimumab plus chemotherapy compared to those who received chemotherapy. The median OS was 14.1 months in the experimental arm versus 10.7 months with chemotherapy (HR, 0.69; 96.71% CI, 0.55-0.87). The most common (20% or more) AEs were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.³

_References:

_{1. Paz-Ares LG, Ciuleanu TE, Lee JS, 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. J Clin Oncol. 2021;39(suppl 15):9016. doi:10.1200/JCO.2021.39.15_suppl.9016}

_{2. FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥ 1%). News release. FDA. May 15, 2020. Accessed June 4, 2021. https://bit.ly/2SYFQLY}

_{3. FDA approves nivolumab plus ipilimumab and chemotherapy for first-line treatment mNSCLC. News release. FDA. May 26, 2020. Accessed June 4, 2021. https://bit.ly/3wZaO5u}