A combination of Bristol-Meyer Squibb‘s Opdivo (nivolumab) and Yervoy (ipilimumab) is more effective than either of the treatments alone as a first-line therapy for patients with advanced melanoma, according to a Phase 3 clinical trial.
The study compared both the treatments alone and in combination. Patients receiving the latter showed higher overall survival, response to treatment, and treatment-free survival after four years of follow-up.
Trial findings were recently discussed in a presentation, titled “Overall survival at 4 years of follow-up in a phase 3 trial of nivolumab plus ipilimumab combination therapy in advanced melanoma (CheckMate 067),” during the European Society for Medical Oncology 2018 Congress in Munich. They were also published in The Lancet Oncology journal.
This four-year update of the CheckMate 067 trial (NCT01844505) represents the longest follow-up of a Phase 3 study evaluating a combination of checkpoint inhibitor therapies.
The trial enrolled 945 adults with advanced or metastatic melanoma who had never received treatment and were ineligible for surgery. Participants were randomly assigned Opdivo, Yervoy, or a combination of the two.
Primary objectives were survival without disease progression and overall survival. Secondary goals included safety, objective response rate, survival and progression-free survival based on PD-L1 levels — a biomarker or response to PD-1/PD-L1 inhibitors like Opdivo.
Previous results from CheckMate 067 showed that the combination was significantly better than any of the medicines alone at extending the time patients lived without disease progression, and increasing survival times. More patients also responded to the combination.
These results led the European Medicines Agency to approve the combination in 2016 for advanced melanoma patients, which was the first approval of a combination of two immuno-oncology agents.
Now researchers report that the Opdivo-Yervoy combination also reduced the risk of death in the long term, with more than half of the patients (53%) living past the four-year mark, compared with 46% for Opdivo and 30% for Yervoy alone.
More patients responded to the combination (58%) than to Opdivo (45%) or Yervoy (19%) alone, consistent with the prior three-year analysis. However, complete responses kept increasing over the years, with 21% of patients on the combination experiencing complete tumor clearance, versus 18% for Opdivo and 5% for Yervoy.
The combination was also significantly better at extending the time patients lived without requiring another therapy. While 71% of those who had taken the combination remained alive without needing an additional therapy after four years, only 50% of those on Opdivo and 39% of patients on Yervoy did.
“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 … to combat this aggressive form of melanoma,” trial investigator F. Stephen Hodi, MD, said in a press release.
“To the best of our knowledge, we have not seen a 53% overall survival rate with any available treatment at four years of follow-up in a randomized setting,” said Hodi, who is the director of the Melanoma Center at Dana-Farber Cancer Institute and an investigator at the Ludwig Center at Harvard Medical School.
Adverse events occurred in 96% of patients treated with the combination, and in 86% of those treated with either medicine alone. The most common adverse events were diarrhea, colon inflammation, and high levels of lipase — a liver enzyme. This data remained unchanged from previous reports.
“These latest results from CheckMate -067 provide further support of the long-term scientific rationale for combining Opdivo and Yervoy for the treatment of advanced melanoma,” said Arvin Yang, MD, PhD, development lead, melanoma, and genitourinary cancers, Bristol-Myers Squibb. “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 healthcare professionals and patients with a durable and safe treatment option.”