First-line Nivolumab and Ipilimumab Plus Chemotherapy Improves OS in NSCLC

Combination nivolumab and ipilimumab has demonstrated efficacy in the first-line setting for non–small cell lung cancer (NSCLC), and recently published results from the ongoing CheckMate 9LA trial (NCT03215706) show that adding a limited course of chemotherapy to the combination treatment is effective and tolerable.¹

The combination of nivolumab plus ipilimumab and chemotherapy was approved by the FDA on May 26, 2020, as a first-line treatment for metastatic or recurrent NSCLC cancer with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations. The application was approved based on CheckMate 9LA data 2 months ahead of schedule after being granted priority review and fast track designation by the FDA.²

The randomized, open-label, phase 3 CheckMate 9LA trial enrolled 1150 patients at 103 hospitals in 19 countries between August 24, 2017 and January 30, 2019. Patients aged 18 years or older with treatment-naïve stage IV or recurrent NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible.

Of the 1150 enrolled patients, 719 were randomized to receive either 4 cycles of chemotherapy alone (n = 358) or nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) with 2 cycles of histology-based, platinum doublet chemotherapy (n = 361). The primary end point was overall survival (OS).

At an interim analysis after a median follow-up of 9.7 months, OS in the combination therapy cohort was significantly longer than in the chemotherapy control group (median OS 14.1 months [95% CI, 13.2-16.2] vs 10.7 months [95% CI, 9.5-12.4], respectively). At an additional 3.5 months of follow-up (median 13.2 months), the nivolumab and ipilimumab plus chemotherapy cohort had a median OS of 15.6 months (95% CI, 13.9-20), while the chemotherapy alone group had a median OS of 10.9 months (95% CI, 9.5-12.6).

Neutropenia, anemia, diarrhea, increased lipase, and asthenia were the most common grade 3 or 4 treatment-related adverse events (TRAEs). In the combination therapy group, 7% had grade 3 or 4 neutropenia, 6% had anemia, 4% had diarrhea, 6% saw increased lipase, and 1% had asthenia. In the chemotherapy alone group, those grade 3-4 TRAEs occurred in 9%, 14%, 1%, 1%, and 2% of patients, respectively.

Serious TRAEs of any grade affected 30% of patients in the combination therapy group, compared with 18% of the control group. There were 7 treatment-related deaths in the nivolumab and ipilimumab plus chemotherapy cohort and 6 in the control group.

The authors concluded that the data support using nivolumab plus ipilimumab with 2 cycles of chemotherapy as a first-line treatment option for advanced NSCLC. Those patients saw significant improvement in OS versus patients given chemotherapy alone, and the risk-benefit profile was favorable, they wrote.

References

1. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. Published online January 18, 2021. doi:10.1016/S1470-2045(20)30641-0

2. FDA approves nivolumab plus ipilimumab and chemotherapy for first-line treatment of metastatic NSCLC. U.S. Food & Drug Administration. Published May 27, 2020. Accessed January 22, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-plus-ipilimumab-and-chemotherapy-first-line-treatment-metastatic-nsclc