Using Indirect Comparisons of Prospective, Randomized Trials to Make Therapeutic Decisions in Melanoma: Cross-Trial Comparisons as Surrogates for Proper Head-To-Head Studies?
Menée à partir des données de deux essais incluant un total de 636 patients atteints d'un mélanome de stade avancé, cette étude compare l'efficacité, du point de vue de la survie sans progression, du taux de réponse objective, de la survie spécifique et de la survie globale, et la toxicité de deux stratégies de première ligne à base de nivolumab, l'une en combinaison avec le relatlimab, l'autre en combinaison avec l'ipilimumab
Patients with metastatic cutaneous melanoma have several options for first-line therapy, with robust evidence-based current guidelines providing strong support for one of three general immunotherapy strategies (CTLA-4 plus PD-1 blockade followed by anti–PD-1 alone, 2-year regimen; LAG3 plus PD-1 blockade, continuous therapy; or one of two approved anti–PD-1 antibodies, 2-year regimen). Patients without a targeted therapy option may be treated second line with additional immunotherapy, using a combination of ipilimumab and nivolumab, and for patients whose melanoma carries a BRAF activating mutation, there are three approved doublets of BRAF and MEK inhibitor that can be used in the first, second, or later line. Patients with limited-volume metastases that can be safely accessed for direct injection also have the option of intralesional talimogene laherparepvec in any line of therapy. The relative safety and activity of double-agent immunotherapy combinations versus single-agent PD-1 blockade was investigated in two large randomized studies reported in 2015 and 2022, respectively.1,2 While the earlier study (Checkmate-067) was statistically powered to detect a significant difference in outcomes for ipilimumab plus nivolumab versus ipilimumab alone, and not to compare the doublet with nivolumab, the more recent study (Relativity-047) compared only relatlimab plus nivolumab with nivolumab alone. However, subset analyses and additional analysis of these and other correlative trial data left important unanswered questions about how to select optimal therapy for each individual patient with advanced cutaneous melanoma.