Opdivo Alone, or Combined with Yervoy Shows Continued Survival Benefit in Advanced Skin Cancer

After six and a half years of follow-up, treatment with Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab) continued to be associated with long-term survival benefits compared to Yervoy alone in patients with previously untreated advanced melanoma, according to findings presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

The long-term data showed that the median overall survival (time that a patient with cancer is still alive) with the combination of Opdivo and Yervoy was 72.1 months and 36.9 months with Opdivo alone, compared with 19.9 months with Yervoy alone. This is reportedly the longest median overall survival in a phase 3 clinical trial of advanced melanoma.

Additionally, the 6.5-year progression-free survival (time during and after treatment when the patient lives without disease progression) rate was 34% with Opdivo and Yervoy and the median progression free survival was 11.5 months. The rates were 29% and 7% with Opdivo and Yervoy as single agents, respectively; the median progression-free survival was 6.9 months and 2.9 months, respectively.

“The sustained (overall survival) and (progression free survival) benefit shown with (Opdivo)-based treatment, particularly the (Opdivo) plus (Yervoy) combination, has changed the way we look at long-term efficacy outcomes for patients with advanced melanoma,” lead study author Dr. Jedd D. Wolchok, chief of the Immuno-Oncology Service, Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center in New York, stated in a news release. “These new results … with nearly half of patients treated with the (Opdivo) and (Yervoy) combination surviving to 6.5 years, confirm the durable, sustained benefit of the combination in patients with advanced melanoma.”

In 2015, the Food and Drug Administration approved the combination of Opdivo and Yervoy for the treatment of patients with metastatic melanoma, based on earlier findings from CheckMate-067. Opdivo is also approved for use as a single agent in this patient population.

In the double-blind, phase 3 CheckMate-067 study, investigators randomized patients with previously untreated unresectable advanced (stage 3 or 4) melanoma 1:1:1 to receive the combination of Opdivo at 1 mg/kg and Yervoy at 3 mg/kg for four doses, followed by Opdivo at 3 mg/kg every two weeks (314 patients), Opdivo alone at 3 mg/kg every two weeks plus placebo (316 patients), or Yervoy alone at 3 mg/kg every three weeks for four doses plus placebo (315 patients). Treatment was administered until disease progression or unacceptable toxicity.

Assessing progression-free survival and overall survival was the main goal of the study. Additional goals included objective response rate (the rate of a measurable response to the treatment) and safety.

At the 6.5-year analysis, 49% of patients were alive and in follow-up. Of this percentage, 77% of patients who were treated with Opdivo plus Yervoy were reported to be off of therapy and did not receive subsequent systemic treatment. Sixty-nine percent of those on Opdivo alone, and 43% of those on single-agent Yervoy also have been off of treatment and did not require subsequent systemic therapy.

The clinical benefit was sustained and observed with both Opdivo and Yervoy combination and Opdivo alone across relevant subgroups, which included those with BRAF-mutant and BRAF wild-type tumors, and patients with baseline liver metastases.

In patients with BRAF wild-type melanoma, the overall survival rate was 46% in those who received the combination, 42% for Opdivo alone, and 22% for Yervoy alone. In those with liver metastases, the overall survival rates were 38%, 31%, and 22% for the combination, Opdivo monotherapy, and Yervoy monotherapy, respectively.

In the combination group, as well as in the single-agent Opdivo group, the median duration of response (length of time a tumor continues to respond to treatment without the cancer growing or spreading) has still not yet been reached and was 19.2 months for those receiving single-agent Yervoy.

Regarding safety, the profile of Opdivo combined with Yervoy was found to be consistent with prior data of the regimen and no new safety signals were observed. No additional treatment-related deaths had occurred since the five-year analysis of CheckMate-067.

Serious or severe side effects occurred in 59% of patients in the Opdivo and Yervoy combination group, in 24% in the Opdivo group, and in 28% of patients in the Yervoy group.

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