Long-term results from ground-breaking melanoma trials

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

In the phase 3 CheckMate 067 trial (NCT01844505), first-line treatment with nivolumab plus ipilimumab or nivolumab alone demonstrated a durable and sustained survival benefit compared with ipilimumab alone in patients with unresectable stage III or IV melanoma [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 randomised to nivolumab plus ipilimumab, nivolumab alone, or ipilimumab alone, 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 intervals following study therapy discontinuation were 27.6 months, 2.3 months, and 1.9 months, respectively.

Prof. Reinhard Dummer (University Hospital Zürich, Switzerland) reported on a 5-year update from the COLUMBUS trial [5]. In this trial, 577 patients were randomised 1:1:1 to encorafenib plus either binimetinib, encorafenib, or vemurafenib. Median overall survival was 33.6 months, 23.5 months and 16.9 months, respectively. At 5 years, the overall survival rates were 34.7%, 34.9%, and 21.4% respectively. Objective response rates were 64.1%, 51.5%, and 40.8%, respectively.

Prof. Georgina Long (Melanoma Institute, Australia) presented the 5-year overall survival data from the ABC trial [6]. In this randomised 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 compared with 26.1 months in the nivolumab arm. At 5 years, overall survival rates were 51% and 34%, respectively. Intracranial progression-free survival rates were 52% and 14%, respectively.

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   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. Abstract 9506, ASCO 2021 Virtual Meeting, 4–8 June.
   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. Abstract 9507, ASCO 2021 Virtual Meeting, 4–8 June.
   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). Abstract 9508, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August, 202123 December, 2021