Five-Year Data Reinforce Survival Benefit of Opdivo/Yervoy in Advanced Lung Cancer

After five years, combination treatment with Opdivo (nivolumab) plus Yervoy (ipilimumab) and chemotherapy continues to provide a survival advantage for people with metastatic non-small cell lung cancer (NSCLC), according to follow-up data from the CheckMate 9LA trial. Five-year efficacy and safety outcomes, which were recently published in the European Journal of Cancer, highlight the durable effects of this immunotherapy-based approach over chemotherapy alone in patients with advanced NSCLC.

Opdivo (Bristol Myers Squibb) is an immunotherapy drug, meaning it uses the body’s immune system to fight cancer. Initially FDA-approved in 2014, Opdivo’s list of indications has expanded over time to treat various types of cancer, including both operable and advanced (metastatic) NSCLC. It is often used as part of a combination approach that includes Yervoy, chemotherapy, and, when possible, surgery.

The CheckMate 9LA study, a phase 3 clinical trial, included 719 patients with metastatic NSCLC. Participants were randomly assigned to receive either the dual immunotherapy-chemotherapy regimen or chemotherapy alone.

Martin Reck, M.D., Ph.D.

For the five-year update, a group of researchers including first author Martin Reck, M.D., Ph.D., at the German Center for Lung Research in Grosshansdorf, Germany, followed patients to see if the combination of Opdivo and Yervoy, given with two cycles of chemotherapy, worked better than four cycles of chemotherapy alone. The researchers also analyzed outcomes for specific groups, including patients who stopped the treatment early due to side effects, those who completed two full years of immunotherapy, patients with brain metastases at the start, and those who survived to the five-year mark.

After a minimum follow-up of 57.3 months, results showed that patients on the combination treatment had higher five-year overall survival (OS) rates. Specifically, 18% of those in the immunotherapy-chemotherapy group were still alive at five years, compared with 11% in the chemotherapy-only group. This overall survival benefit was consistent across different tumor types and patient subgroups.

Subgroup analyses further highlighted the combination treatment’s potential. Among patients with low PD-L1 expression, five-year overall survival was 22% with the combination treatment, compared with 8% with chemotherapy alone. Patients with squamous cell histology also showed benefits, with a five-year overall survival rate of 18% for those on the combination regimen versus 7% for chemotherapy alone. Patients with baseline brain metastases also had improved outcomes with an overall survival rate of 20%, compared with 6% in the chemotherapy group.

The trial also examined the durability of the treatment response. Among patients who responded to the combination therapy, 19% maintained their response at five years, compared with 8% in the chemotherapy group. Analyses revealed no new concerning safety signals in five-year survivors.

Notably, patients who discontinued treatment due to side effects also showed favorable outcomes, with 37% still alive at the five-year mark.

Those who completed two full years of treatment saw even greater survival benefits, with most still alive, treatment-free, and still responding at five years. These results show that the combination treatment offers lasting benefits, whether or not patients completed the full course.

“Taken together, these data further reinforce nivolumab [Opdivo] plus ipilimumab [Yervoy] with chemotherapy as an efficacious first-line treatment option for patients with mNSCLC,” the authors wrote in their conclusion.

Funding for the trial was provided by Bristol Myers Squibb.