Nivolumab regimen improves OS in metastatic non-small cell lung cancer
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First-line nivolumab with ipilimumab and a limited chemotherapy course significantly improved OS among patients with metastatic non-small cell lung cancer, according to study results presented during the ASCO20 Virtual Scientific Program.
Martin Reck, MD, PhD, head of the department of thoracic oncology and its clinical trial department at Lung Clinic Grosshansdorf in Germany, and colleagues observed no new safety signals with the regimen during the randomized phase 3 CheckMate-9LA trial.
Results of part 1 of the CheckMate 227 study showed nivolumab (Opdivo, Bristol-Myers Squibb) — an anti-PD-1 antibody, in combination with ipilimumab (Yervoy, Bristol-Myers Squibb) — an anti-CTLA-4 antibody, improved OS and durability of response compared with standard chemotherapy as first-line treatment for advanced NSCLC regardless of PD-L1 expression.
Reck and colleagues hypothesized that adding a limited course of chemotherapy to the combination may provide disease control and build on the OS benefits conferred by dual PD-1 and CTLA-4 inhibition.
CheckMate-9LA included 719 treatment-naive patients with stage IV/recurrent NSCLC and no known sensitizing EGFR or ALK alterations.
Researchers randomly assigned 361 patients to nivolumab dosed at 360 mg three times per week in combination with ipilimumab dosed at 1 mg/kg six times per week and two cycles of chemotherapy. Immunotherapy treatment continued until for 2 years, or until disease progression or unacceptable toxicity.
The other 358 patients received four cycles of chemotherapy alone. Patients with nonsquamous NSCLC assigned chemotherapy alone had the option to receive pemetrexed maintenance therapy.
Investigators stratified patients by PD-L1 status, sex and histology.
OS served as the primary endpoint. PFS and objective response rate by blinded independent central review, as well as efficacy by PD-L1 subgroups, served as secondary endpoints. Safety and tolerability served as exploratory endpoints.
Results of a preplanned interim analysis — based on minimum follow-up of 8.1 months — showed significantly longer OS in the combination group than in the chemotherapy-only group (HR = 0.69; 96.71% CI, 0.55-0.87), as well as statistically significant improvements in ORR and PFS.
After minimum follow-up of 12.7 months, the combination continued to confer an OS benefit (15.6 months vs. 10.9 months; HR = 0.66; 95% CI, 0.55-0.8). A higher percentage of patients assigned the nivolumab-ipilimumab regimen survived at least 1 year (63% vs. 47%).
Clinical benefit appeared consistent across all efficacy measures and in all key subgroups, including those based on PD-L1 expression and histology.
Researchers reported grade 3 and grade 4 treatment-related adverse events among 47% of patients assigned the combination and 38% of patients assigned chemotherapy alone.
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Reck M, et al. Abstract 9501. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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