Updated results from the Phase 3 CheckMate -238 trial evaluating Opdivo (nivolumab, Bristol-Myers Squibb Company) versus Yervoy (ipilimumab, Bristol-Myers Squibb Company) in patients with stage IIIB/C or stage IV melanoma who are at high risk of recurrence following complete surgical resection show that Opdivo continued to demonstrate statistically longer recurrence-free survival (RFS) of 62.6%. Recurrence-free survival was 50.2% for Yervoy (HR: 0.66, P<0.0001) at a minimum follow-up of 24 months across key subgroups, including disease stages and BRAF mutation status. Recurrence-free survival was the primary endpoint of the study.
No new safety data were generated as part of the 24-month analysis. As previously reported from the 18-month analysis, Opdivo demonstrated a significantly lower rate of adverse events (AEs) leading to discontinuation (9.7% of patients in the Opdivo arm compared to 42.6% of patients in the Yervoy arm) and treatment-related grade 3/4 AEs (14.4% of patients in the Opdivo arm compared to 45.9% in the Yervoy arm).
Findings were presented during the Melanoma/Skin Cancers session at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018 in Chicago (Abstract #9502).
“The broader use of Immuno-Oncology agents has changed the cancer treatment landscape and, with advances in research, we have been able to extend the use of these agents to adjuvant therapy in melanoma in order to help prevent disease recurrence,” noted Jeffrey S. Weber, MD, PhD, principal investigator of CheckMate -238. “Results from the study’s 24-month follow-up, the longest follow-up of any PD-1 inhibitor in the adjuvant setting, continue to strongly support the benefit of nivolumab across multiple stages of melanoma and BRAF mutation status.”
Arvin Yang, MD, PhD, development lead, melanoma and genitourinary cancers, Bristol-Myers Squibb, said, “The updated CheckMate -238 data continue to show that adjuvant treatment can change the course of melanoma by preventing relapse and progression to an advanced stage.”
Additional Data from CheckMate -238 at ASCO 2018
In the study, Opdivo demonstrated superior RFS versus Yervoy, regardless of disease stage, PD-L1 expression or BRAF mutation status, with RFS rates of 62.6% with Opdivo compared to 50.2% with Yervoy in the intent-to-treat patient population. In patients with stage IIIB melanoma, RFS rates at 24 months for Opdivo were 70.8% versus 60.7% with Yervoy; for patients with stage IIIC melanoma, RFS rates were 58.0% with Opdivo versus 45.4% with Yervoy; and for patients with stage IV melanoma, RFS rates for Opdivo were 58.0% versus 44.3% with Yervoy. In patients with BRAF mutant melanoma, RFS rates for Opdivo were 61.9% versus 51.7% with Yervoy; in patients with BRAF wild-type melanoma, Opdivo demonstrated a RFS of 63.5% versus 46.2% with Yervoy.
About CheckMate -238
CheckMate -238 is an ongoing Phase 3, randomized double-blind study of Opdivo versus Yervoy in patients who have undergone complete resection of stage IIIB/C or stage IV melanoma. The trial randomized 906 patients 1:1 to receive either Opdivo 3 mg/kg every two weeks (n=453) or Yervoy 10 mg/kg (n=453) every three weeks for four doses and then every 12 weeks starting at week 24. Patients were treated until disease recurrence, unacceptable toxicity or withdrawal of consent for up to one year. The primary endpoint is RFS, defined as the time between randomization and the date of first recurrence, new primary melanoma or death. After meeting the primary endpoint, the trial will continue to evaluate for overall survival, a secondary endpoint.