Immunotherapy Combo Shows Durable Four-Year Survival Benefit in Advanced Melanoma

The combination use of two immunotherapy agents in the first-line setting helped patients with advanced melanoma live longer compared with treatment with either drug alone, according to study findings published in The Lancet Oncology.

In the double-blind, randomized phase 3 CheckMate-067 trial, 945 patients with previously untreated, unresectable stage 3 or stage 4 melanoma were randomly assigned to be treated with Opdivo (nivolumab) plus Yervoy (ipilimumab; 314 patients), Opdivo (316 patients) alone or Yervoy (315 patients) alone.

The findings showed that more than half (53 percent) of patients lived for four years following their diagnosis when they received Opdivo and Yervoy together, compared with those given either Opdivo or Yervoy along (46 percent and 30 percent, respectively).

“These four-year results from CheckMate 067, which represent the longest follow-up to date for patients receiving combination therapy with nivolumab and ipilimumab, enhance our understanding of the potential long-term survival benefits of combination therapy, regardless of PD-L1 expression levels, to combat this aggressive form of melanoma,” F. Stephen Hodi, M.D., director of the Melanoma Center at Dana-Farber Cancer Institute, and investigator at the Ludwig Center at Harvard, both in Boston, said in a press release.

“To the best of our knowledge, we have not seen a 53 percent overall survival rate with any available treatment at four years of follow-up in a randomized setting,” he added.

In addition, the rates of people who saw all signs of cancer disappear after treatment continued to increase, noted researchers. The complete response rate in the combination group was 21 percent, 18 percent for Opdivo alone and 5 percent for Yervoy alone.

The four-year follow-up also showed that more patients were treatment-free in the combination arm (71 percent) compared with those who received single agents Opdivo (50 percent) or Yervoy (39 percent).

Patients in all the groups experienced treatment-related grade 3/4 side effects. Diarrhea was the most common grade 3 side effect seen in the combination group (9 percent) and in the Opdivo monotherapy group (3 percent),while colitis (inflammation in the digestive tract) was the most common in the Yervoy monotherapy group (7 percent).

All three groups (5 percent in the Opdivo/Yervoy arm; 3 percent in Opdivo arm; and 1 percent in Yervoy arm) saw increased lipase levels, which is a grade 4 side effect. Lipase is a protein released by the pancreas and helps to absorb fats in the body. If too much is released, the pancreas can become inflamed.

Researchers noted that four treatment-related deaths occurred over the course of the study: two in the combination group, one in the Opdivo group and one in the Yervoy group.

Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. This year more than 91,000 new melanomas will be diagnosed, mainly in men, in the United States.

“This study advances our mission of understanding how we can best harness the body’s immune system to fight this aggressive form of cancer and provide health care professionals and patients with a durable and safe treatment option,” said Arvin Yang, M.D., Ph.D., development lead of melanoma and genitourinary cancers at Bristol-Myers Squibb, the maker of both cancer immunotherapies.