Nivolumab plus ipilimumab demonstrated long-term efficacy in patients with advanced non-small cell lung cancer (NSCLC), according to updated results from the CheckMate 227 trial published in the Journal of Thoracic Oncology.1
Patients treated with nivolumab plus ipilimumab had superior overall survival (OS), compared with patients who received platinum chemotherapy, after the patients had been off study treatment for at least 2 years.
In part 1 of the phase 3 trial (ClinicalTrials.gov Identifier: NCT02477826), researchers investigated nivolumab-based regimens in patients with recurrent or stage IV NSCLC who had received no prior systemic anticancer therapy.
The study included 1189 patients with PD-L1 expression levels of 1% or higher who were randomly assigned to nivolumab plus ipilimumab (n=396), nivolumab monotherapy (n=396), or platinum-doublet chemotherapy (n=397).
The study also included 550 patients with PD-L1 expression below 1% who were randomly assigned to nivolumab plus ipilimumab (n=187), nivolumab plus platinum-doublet chemotherapy (n=177), or platinum-doublet chemotherapy alone (n=186).
Patients received treatment until disease progression or unacceptable toxicity, or for up to 2 years for immunotherapy. In the primary analysis, nivolumab plus ipilimumab prolonged OS when compared with chemotherapy alone, regardless of PD-L1 expression.2
For the current analysis, all patients treated with nivolumab-based regimens had been off study treatment for at least 2 years. One patient who received chemotherapy alone was still receiving pemetrexed maintenance.
Among patients who progressed (in both PD-L1 cohorts), 165 patients (38%) in the nivolumab-ipilimumab arms received subsequent systemic anticancer therapies and 32 patients (7%) received subsequent immunotherapy. In the chemotherapy arms, 215 patients (48%) received subsequent systemic anticancer therapies and 166 (38%) received subsequent immunotherapy.
At a median follow-up of 54.8 months (minimum, 49.4 months), there was a continued OS benefit among patients who received nivolumab plus ipilimumab, regardless of PD-L1 expression.
Among patients with PD-L1 expression of 1% or higher, the 4-year OS rate was 29% in the nivolumab-ipilimumab arm and 18% in the chemotherapy-alone arm (HR, 0.76; 95% CI, 0.65-0.90). The 4-year progression-free survival (PFS) rate was 14% and 4%, respectively.
In patients with PD-L1 expression below 1%, the 4-year OS rate was 24% in the nivolumab-ipilimumab arm and 10% in the chemotherapy-alone arm (HR, 0.64; 95% CI, 0.51-0.81). The 4-year PFS rate was 12% and 0%, respectively.
In all treatment arms, the incidence of any-grade treatment-related adverse events (TRAEs), grade 3-4 TRAEs, serious TRAEs, and TRAEs leading to discontinuation were largely unchanged, according to the researchers.
“These results continue to support nivolumab plus ipilimumab as a first-line treatment option in patients with advanced NSCLC,” the researchers wrote.
Disclosures: This research was supported by Bristol Myers Squibb and Ono Pharmaceutical Company Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Paz-Ares LG, Ramalingam SS, Ciuleanu TE, et al. First-Line nivolumab plus ipilimumab in advanced non-small cell lung cancer: 4-Year outcomes from the randomized, open-label, phase 3 CheckMate 227 part 1 trial. J Thorac Oncol. Published online October 11, 2021. doi:10.1016/j.jtho.2021.09.010
- Hellmann MD, Paz-Ares L, Caro RB, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020-2031. doi:10.1056/NEJMoa1910231