After initial results over 5 years ago, long-term follow-up data from 3 clinical trials – CheckMate 067, COLUMBUS, and ABC – show a durable and sustained clinical benefit for patients with melanoma.

In the phase 3 CheckMate 067 trial (NCT01844505), a durable and sustained survival benefit was demonstrated in patients with unresectable stage III or IV melanoma when treated in first line with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab alone [1].

Results from the phase 3 COLUMBUS trial (NCT01909453) showed improved survival of patients with advanced/metastatic BRAF V600-mutant melanoma when treated in first line with encorafenib plus binimetinib versus encorafenib (or vemurafenib) [2]. The phase 2 ABC trial (NCT02374242) showed good intracranial responses in melanoma patients with asymptomatic brain metastases [3]. Now, long-term follow-up data of these trials are available. Dr Jedd Wolchok (Memorial Sloan Kettering Cancer Center, NY, USA) presented overall survival data of the CheckMate 067 trial [4].

At the time of analysis, all patients (n=945), who were 1:1:1 randomized to nivolumab plus ipilimumab, nivolumab, or ipilimumab, had a minimum follow-up of 6.5 years. Median overall survival was 72.1 months with nivolumab plus ipilimumab, 36.9 months with nivolumab, and 19.9 months with ipilimumab. Survival rates at 6.5 years were 49%, 42%, and 23%, respectively. Survival rates at 6.5 years in BRAF-mutated patients were 57%, 43%, and 25%, respectively. Median treatment-free interval following study therapy discontinuation were 27.6 months, 2.3 months, and 1.9 months, respectively. “

These results show durable improved outcomes with nivolumab plus ipilimumab and nivolumab monotherapy versus ipilimumab monotherapy in patients with advanced melanoma”, concluded Dr Wolchok. Prof. Reinhard Dummer (University Hospital Zürich, Switzerland) reported a 5-year update from the COLUMBUS trial [5]. In this trial, 577 patients were randomized 1:1:1 to encorafenib plus binimetinib, encorafenib, or vemurafenib. Median overall survival was 33.6 months, 23.5 months, and 16.9 months, respectively. The 5-year overall survival rate was 34.7%, 34.9%, and 21.4% respectively. Objective response rate was 64.1%, 51.5%, and 40.8%, respectively. “These updated results confirm long-term benefits of encorafenib plus binimetinib in the first line for patients with BRAF-mutated melanoma”, concluded Prof. Dummer. Prof. Georgina Long (Melanoma Institute, Australia) presented 5-year overall survival data from the ABC trial. In this randomized phase 2 trial, melanoma patients with untreated brain metastases were treated with nivolumab plus ipilimumab (n=35) or nivolumab (n=25).

Median overall survival in the nivolumab plus ipilimumab arm was not reached versus 26.1 months in the nivolumab arm. Overall survival rate at 5 years was 51% and 34%, respectively. Intracranial progression-free survival rate at 5 years was 52% and 14%, respectively. “Nivolumab combined with ipilimumab has high activity and durability in asymptomatic melanoma brain metastases, and may be considered for upfront therapy in such patients”, concluded Prof. Long.

  1. Wolchok JD, et al. N Engl J Med 2017; 377:1345-1356.
  2. Dummer R, et al. Lancet Oncol. 2018; 19: 1315-1327.
  3. Long GV, et al. Lancet Oncol. 2018; 19: 672-681.
  4. Wolchok JD, et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. ASCO 2021 Virtual Meeting, abstract 9506.
  5. Dummer R, et al. Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma. ASCO 2021 Virtual Meeting, abstract 9507.
  6. Long GV, et al. Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets).ASCO 2021 Virtual Meeting, abstract 9508.

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