New First-Line Treatment Option for NSCLC: Nivolumab + Ipilimumab + Chemotherapy

First-line treatment with nivolumab in combination with ipilimumab and chemotherapy continued to provide a durable survival benefit compared with chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC), according to results from a 2-year follow-up of the CheckMate 9LA trial presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Nivolumab and ipilimumab have distinct but complementary mechanisms of action, and combination treatment with these 2 agents had shown improved long-term survival benefits in several different cancers.

In the randomized, open-label, phase 3 CheckMate 9LA trial (ClinicalTrials.gov Identifier: NCT03215706), first-line nivolumab plus ipilimumab combined with 2 cycles of chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared with standard chemotherapy alone (4 cycles) in patients with advanced NSCLC.

Martin Reck, MD, PhD, of the Airway Research Center North, German Center for Lung Research, LungClinic in Germany, presented updated efficacy and safety results from the CheckMate 9LA trial with a minimum follow-up of 2 years, and a post hoc efficacy analysis in patients who discontinued nivolumab plus ipilimumab combined with chemotherapy due to treatment-related adverse events (TRAEs).

The study included 719 participants with histologically confirmed stage IV or recurrent NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status 1 or less, and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations. The participants were stratified based on the expression of PD-L1, sex, and squamous or non-squamous histology.

The patients were randomly assigned 1:1 to receive nivolumab plus ipilimumab combined with chemotherapy (361 patients) or chemotherapy alone (358 patients). Patients with non-squamous NSCLC in the chemotherapy arm were allowed to receive pemetrexed as maintenance therapy. The primary endpoint was OS. The secondary endpoints were PFS, ORR by blinded independent central review, and efficacy based on the expression of PD-L1 levels.

At a median follow-up of at least 24.4 months, patients treated with nivolumab plus ipilimumab combined with chemotherapy continued to derive OS benefit compared with patients receiving chemotherapy alone. The median OS was 15.8 months in the nivolumab-ipilimumab-chemotherapy arm and 11.0 months in the chemotherapy arm (hazard ratio [HR] 0.72; 95% CI, 0.61-0.86). The 2-year OS rate was 38% and 26%, respectively.

The overall survival benefit was similar with nivolumab-ipilimumab-chemotherapy across different PD-L1 expression levels and histologies.

The median PFS was 6.7 months in the nivolumab-ipilimumab-chemotherapy arm and 5.3 months in the chemotherapy arm (hazard ratio [HR] 0.67; 95% CI, 0.56-0.79). In the nivolumab-ipilimumab-chemotherapy arm, 8% of patients had disease progression and received subsequent immunotherapy, compared with 37% of patients in the chemotherapy arm.

The ORR was 38% in the nivolumab-ipilimumab-chemotherapy arm and 25% in the chemotherapy arm.

TRAEs occurred in 92% of patients in the nivolumab-ipilimumab-chemotherapy arm and 48% of patients in the chemotherapy arm. Grade 3 to 4 TRAEs occurred in 48% and 38%, respectively. No new safety signals were observed during the extended 2-year follow-up.

“In a post hoc analysis, discontinuation of nivolumab plus ipilimumab plus chemotherapy due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients. Fifty-six percent of the responders who had discontinued treatment due to TRAEs maintained their responses for more than 1 year after treatment discontinuation,” Dr Reck said during his presentation. “These updated results continue to support nivolumab plus ipilimumab plus 2 cycles of chemotherapy as an efficacious first-line treatment option for patients with advanced NSCLC.”

Disclosures: This study was funded by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Reck M, Ciuleanu TE, Cobo M, et al. First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA. J Clin Oncol. 2021;39: (suppl 15; abstr 9000). doi:10.1200/JCO.2021.39.15_suppl.9000

This article originally appeared on Cancer Therapy Advisor