Treatment with the immune-oncology agents Opdivo (nivolumab) and Yervoy (ipilimumab) has demonstrated significantly higher cure rates in patients with resected stage 3 or 4 melanoma compared to placebo, according to a recent analysis published in the Journal of Clinical Oncology. The study combined data from the CheckMate 238 and EORTC 18071 trials to estimate long-term survivorship rates.
Superior Cure Rates with Opdivo
The analysis indicated that patients receiving Opdivo were more likely to be cured than those receiving Yervoy, and Yervoy recipients were more likely to be cured than those receiving a placebo. Specifically, patients treated with Opdivo were more than twice as likely to be cured compared to those receiving a placebo.
Study Details and Results
The findings come from a mixture cure model study analysis comparing results from two large phase 3 trials: CheckMate 238 (906 patients) and EORTC 18071 (951 patients). After a minimum follow-up of five years in CheckMate 238, estimated cure rates were 48.3% for patients treated with Opdivo and 38.2% for those treated with Yervoy. In the EORTC 18071 trial, after a median follow-up of 6.9 years, estimated cure rates were 38% for Yervoy and 29.2% for the placebo. An indirect comparison of the two trials showed significantly higher odds of being cured with Opdivo than with the placebo.
Impact of Disease Stage and BRAF Mutation
When focusing solely on stage 3B/3C patients, the estimated five-year cure rates in CheckMate 238 were 46.6% for Opdivo and 39.1% for Yervoy, while in EORTC 18071, the rates were 35.4% for Yervoy and 25.6% for the placebo. Interestingly, excluding stage 4 patients lowered Opdivo's cure rate, potentially due to other factors such as age, sex, and BRAF mutation status.
In CheckMate 238, BRAF-mutant patients had estimated five-year cure rates of 49% for Opdivo and 42% for Yervoy, while BRAF wild-type patients had rates of 41.5% for Opdivo and 34.7% for Yervoy. Opdivo consistently showed an approximate 7% increase in cure rate over Yervoy, regardless of BRAF mutation status.
Factors Influencing Cure Odds
Results from an indirect treatment comparison between each trial indicated that treatment, age, and disease stage (3C) all had a significant effect on the odds of being cured. Stage 3C patients had lower cure odds than stage 3B patients. Sex, trial, and other stage (3A, 4) effects on cure rates were not significant, likely due to small sample sizes.
Treatment Regimens
Treatment regimens consisted of Opdivo 3 milligrams/kilograms (mg/kg) once every two weeks or Yervoy 10 mg/kg once every three weeks for four doses, followed by once every 12 weeks starting at week 24.
