The phase III CheckMate -067 trial continued to demonstrate improved overall survival with the first-line combination of Opdivo (nivolumab) plus Yervoy (ipilimumab), versus Yervoy alone, in patients with advanced metastatic melanoma.
Bristol-Myers Squibb sponsored the study.
With a minimum follow-up of 60 months, five-year overall survival rates were 52% for the Opdivo plus Yervoy combination, 44% for Opdivo alone, and 26% for Yervoy alone. Data from CheckMate -067 was presented at ESMO Sept. 28 and were simultaneously published in The New England Journal of Medicine.
The safety profile for Opdivo plus Yervoy was consistent with prior findings, with no new safety signals and no additional treatment-related deaths. At this five-year analysis, treatment-related adverse events were consistent with those previously reported and occurred in 300 (96%) patients in the combination group, 271 (87%) patients in the Opdivo group, and 268 (86%) patients in the Yervoy group. Grade 3/4 adverse events occurred in 186 (59%), 73 (23%), and 86 (28%) patients, respectively.
The percentage of patients experiencing an objective response remained stable at 58% for Opdivo plus Yervoy, 45% for Opdivo alone, and 19% for Yervoy, while the percentage of patients experiencing a complete response continued to increase, with complete response rates at five years of 22% for Opdivo plus Yervoy, 19% for Opdivo alone, and 6% for Yervoy alone. In addition, the proportion of patients alive and treatment-free was 74% in the Opdivo plus Yervoy group and 58% and 45% for Opdivo alone and Yervoy alone, respectively.
Among patients with BRAF-mutant or wild-type tumors, the rate of overall survival at five years was 60% and 48%, respectively, in patients who received Opdivo plus Yervoy; 46% and 43% for Opdivo alone; and 30% and 25% for Yervoy alone. Health-related quality of life continued to be maintained during or following treatment with Opdivo alone or the combination of Opdivo plus Yervoy.
“Now, with over half of patients treated with the nivolumab plus ipilimumab combination surviving to five years, and 74% of surviving patients remaining treatment-free, we have set a new and encouraging precedent,” CheckMate -067 lead investigator and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, James Larkin, said in a statement.
“The sustained long-term efficacy seen in the five-year CheckMate -067 data demonstrates the importance of dual Immuno-Oncology therapy,” development lead of Melanoma and Genitourinary Cancers at Bristol-Myers Squibb, Arvin Yang, said in a statement.
CheckMate -067 is a phase III, double-blind, randomized trial that evaluated the combination of Opdivo plus Yervoy or Opdivo monotherapy versus Yervoy monotherapy in 945 patients with previously untreated advanced melanoma. Patients in the combination group (n=314) received Opdivo 1 mg/kg plus Yervoy 3 mg/kg (Q3W) for four doses followed by Opdivo 3 mg/kg every two weeks (Q2W). Patients in the Opdivo monotherapy group (n=316) received Opdivo 3 mg/kg Q2W plus placebo. Patients in the Yervoy monotherapy group (n=315) received Yervoy 3 mg/kg every three weeks for four doses plus placebo. Patients were treated until progression or unacceptable toxic effects. Overall survival and progression-free survival were co-primary endpoints of the trial. Secondary endpoints included objective response rates, efficacy by tumor PD-L1 expression level and safety.
