Jeffrey Weber, MD, PhD
Nivolumab (Opdivo) demonstrated a sustained efficacy benefit versus ipilimumab (Yervoy) as an adjuvant therapy in patients with high-risk resected stage III/IV melanoma.
Updated findings from the CheckMate-238 trial, which were presented at the 2018 ASCO Annual Meeting, showed that at a minimum follow-up of 24 months, the recurrence-free survival (RFS) was significantly longer on the nivolumab arm versus the ipilimumab arm. These results extended into each subgroup of disease stage, PD-L1 expression, and BRAF
mutation status, according to Jeffrey S. Weber, MD, PhD, lead study author.
In the study, 906 patients were randomized 1:1 to either 3 mg/kg nivolumab given every 2 weeks, or 10 mg/kg administered every 3 weeks for 4 doses, then every 12 weeks for up to 1 year.
Two-year RFS rates were 62.6% on the nivolumab arm compared with 50.2% on the ipilimumab arm. For patients with stage IV disease, 2-year RFS rates were 58% vs 44.3% for nivolumab and ipilimumab, respectively. In the PD–L1 high subgroup, 2-year RFS rates were 75.5% for patients treated with nivolumab vs 58.4% for those under ipilimumab arms.
Weber added that the toxicity profile favored nivolumab, with 0 treatment-related deaths in that cohort versus 5 in the ipilimumab group.
Based on the 18-month follow-up data of CheckMate-238, the European Commission approved nivolumab as an adjuvant treatment for adult patients with completely resected melanoma with lymph node involvement or metastatic disease, regardless of BRAF
mutation status in July 2018. The FDA approved the PD-1 inhibitor in this setting in December 2017.
In an interview with OncLive
, Weber, deputy director and co-director of the Melanoma Program, NYU Langone’s Perlmutter Cancer Center, and a 2016 Giant of Cancer Care®
in Melanoma, discussed the promise of nivolumab in this setting and a general overview of the melanoma treatment landscape.
OncLive: Please provide some background of the CheckMate-238 trial.
: At the 2018 ASCO Annual Meeting, I reported on the updated results from this large phase III double-blind trial. It had an active control arm. Patients with a high risk of recurrence—50% or higher risk of recurrence beyond 5 years—who also had stage IIIb, IIIc, or IV melanoma, were randomly allocated to either nivolumab, the PD-1 antibody, or ipilimumab, the CTLA-4 antibody.
The primary endpoint of this 1-year interval was RFS. The initial results were presented at the 2017 ESMO Congress, in which there was clearly evidence for benefit in the nivolumab arm compared with the ipilimumab arm. There was significantly less toxicity, I might add.
I presented updated data at the 2018 ASCO Annual Meeting, with an additional 6-plus months of follow-up time. There is still benefit with the nivolumab arm; the toxicity data remain favorable for nivolumab. Just to refresh your memory, the number of patients who stopped treatment due to adverse events (AEs) with nivolumab was 8%; more than 30% stopped treatment on ipilimumab. There is statistically significant benefit here. If you look at the secondary endpoint of metastasis-free survival, there continues to be a benefit at 12 months, 18 months, and now 24 months and beyond for nivolumab. We think there will be an overall survival benefit as well.