Background: phase III, RCT included 906 patients with resected stage IIIB-C (Stage IIIA was not included unlike KEYNOTE-054) or stage IV melanoma, with ECOG 0-1. Brain mets, mucosal or acral melanoma were eligible. Main exclusion: Ocular melanoma, autoimmune disease and systemic steroid use.

Arm A: Nivolumab 3mg/kg IV q2wk (n=453)
Arm B: High dose ipi: ipilimumab 10mg/kg IV q3wk x4 then q12wk wk (n=453)
Treatment duration: up to 1yr or until disease recurrence, unacceptable toxicity, or withdrawal of consent.

Primary end point: RFS
Median Follow up: 51.1mo (4.2yr)

Median RFS: 52.4mo vs 24.1mo; nivolumab and ipilimumab, respectively
4-yr RFS: 51.7% vs 41.2%; nivolumab and ipilimumab, respectively (HR 0.71, 95%CI 0.60-0.86; P=.0003)

Median distant metastasis-free survival (mDMFS): not reached vs 52.9; nivolumab and ipilimumab, respectively
4-yr DMFS: 59.2% vs 53.3%; nivolumab and ipilimumab, respectively
4-yr OS: 77.9% vs 76.6%; nivolumab and ipilimumab, respectively (HR 0.87, 95%CI 0.66-1.14; P=.31)
mOS was not reached in either groups.

Main adverse events. Nivolumab and ipilimumab: any events (4% vs 6%). In nivolumab group of 452 patients 2% had grade 3-4 adverse events: one patient had pneumonitis, one DKA and one diarrhea. In ipilimumab out of 453 patient 2% had grade 3-4 toxicities: colitis (two patients), and diarrhea, rash, elevated lipase, bone marrow failure, immune thrombocytopenic purpura, rash, and adrenocortical insufficiency. Some patients had more than one adverse event

Conclusions: Nivolumab provides significant improvement in PFS in adjuvant settings for resected melanoma patients. Impact on OS has not yet established.

Summarized by Veli Bakalov, MD

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