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Soo Park, MD
Soo Park, MD
Posted: Wednesday, March 6, 2024
Findings from the phase II SECOMBIT trial were recently published in Nature Communications. The article reported the 4-year survival outcomes as well as preliminary biomarkers involved in the long-term effects of first-line immunotherapy in patients with untreated, metastatic BRAF V600–mutant melanoma. Paolo A. Ascierto, MD, of the International Tumor Institute IRCCS “Fondazione G. Pascale,” Naples, Italy, and colleagues found improved survival with immunotherapy followed by BRAF/MEK inhibition. Additionally, they reported a trend toward 4-year overall survival as well as total progression-free survival in patients with loss-of-function mutations in JAK and low baseline serum levels of interferon-gamma (IFN-ƴ).
A total of 209 patients with untreated metastatic BRAF V600–mutant melanoma were randomly assigned to three treatment arms: arm A (encorafenib plus binimetinib until progressive disease, followed by ipilimumab plus nivolumab; n = 69), arm B (ipilimumab plus nivolumab until progressive disease, followed by encorafenib plus binimetinib; n = 71), and arm C (“sandwich,” encorafenib plus binimetinib for 8 weeks, followed by ipilimumab plus nivolumab until progressive disease, followed by encorafenib plus binimetinib; n = 69).
Overall findings revealed the overall survival rates at 3 and 4 years, respectively, were 53% (95% confidence interval [CI] = 41%–65%) and 46% (95% CI = 33%–59%) for arm A, 64% (95% CI = 53%–76%) and 64% (95% CI = 53%–76%) for arm B, and 61% (95% CI = 50%–73%) and 59% (95% CI = 47%–71%) for arm C. Further, progression-free survival rates at 4 years were 29% (95% CI = 18%–40%), 55% (95% CI = 43%–67%), and 54% (95% CI = 42%–66%) for arms A, B, and C, respectively.
Biomarker analyses revealed deleterious mutations in JAK1, JAK2, and JAK3, which were associated with better 4-year overall survival rates than for patients without such mutations. Additionally, patients with low serum IFN-ƴ had better 4-year overall survival rates in arm C.
Disclosure: For full disclosures of the study authors, visit www.nature.com.
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