Adjuvant Opdivo Delays Recurrence in Advanced Melanoma Patients, CheckMate-238 Study Shows

Adjuvant Opdivo Delays Recurrence in Advanced Melanoma Patients, CheckMate-238 Study Shows

Advanced melanoma patients at high risk of recurrence after surgery fare better if given Opdivo (nivolumab) compared to the standard of care Yervoy (ipilimumab), according to data presented at the European Society for Medical Oncology (ESMO) 2017 Congress, in Madrid, Spain.

The findings from the CheckMate -238 Phase 3 trial (NCT02388906), featured in the poster “Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: a randomized, double-blind, phase 3 trial (CheckMate 238),” show that Opdivo delayed disease recurrence compared to Yervoy, and induced fewer side effects.

The research also was published in the New England Journal of Medicine, in a study titled “Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.”

In patients with stage 3 melanoma, where the cancer has spread to the lymph nodes, surgical resection of the primary tumor and affected lymph nodes is required. But despite surgical intervention, most patients will still experience disease recurrence and eventually progress to metastatic melanoma.

To help decrease the risk of relapse after surgery, adjuvant therapy is administered. The term “adjuvant” refers to any therapy given after initial cancer treatment.

Yervoy is the standard-of-care adjuvant therapy for stage 3 melanoma in the U.S., but this approach is still being debated in Europe. But Opdivo also showed encouraging survival results in a pilot study that included 33 stage 3/4 melanoma patients who had undergone surgery.

This led to CheckMate 238, a Phase 3, randomized, double-blind study designed to compare the safety and effectiveness of Opdivo and Yervoy as adjuvant therapies for advanced melanoma patients.

The study, sponsored by Bristol-Myers Squibb, Opdivo and Yervoy’s developer, recruited 906 patients with high risk of relapse over a five-year period. The study’s primary goal was to determine the time to disease recurrence. Overall survival was the secondary endpoint.

At 18 months, 66.4 percent of patients in the Opdivo arm were still alive and recurrence-free, compared to 52.7 percent in the Yervoy group. In addition, Opdivo-treated patients had fewer stage 3/4 side effects —14% vs. 46%.

The trial was to be concluded in November 2019, but due to Opdivo’s promising results, ESMO’s Data Safety Monitoring Committee decided to end it.

“The results of CheckMate 238 are very exciting. They show for the first time that an anti-PD-1 drug is superior in the adjuvant setting and because of its lower toxicity nivolumab is much easier to give than ipilimumab,” John Haanen, MD, PhD, head of the Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, said in a press release. “The same occurs in the metastatic setting where anti-PD-1 treatment is more efficacious and has a much better safety profile and has replaced ipilimumab as first line treatment.”

Nivolumab is an anti-PD-1, which is short for human programmed death receptor-1 blocking antibody. Keytruda (pembrolizumab), another anti-PD-1 drug, also is being tested as an adjuvant therapy in stage 3 melanoma patients. KEYNOTE-054 is a Phase 3 EORTC trial (NCT02362594) testing Keytruda versus placebo. (EORTC stands for European Organisation for Research and Treatment of Cancer.)

“If relapse-free survival is better with pembrolizumab, it is likely that adjuvant anti-PD-1 will become standard of care for high-risk melanoma in the near future, provided an overall survival benefit is also shown,” Haanen said.