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Sequencing of ipilimumab plus nivolumab and encorafenib plus binimetinib for untreated braf-mutated metastatic melanoma (SECOMBIT): a randomized, three-arm, open-label phase II trial

Autores: Ascierto, P. A. (Autor de correspondencia); Mandala, M.; Ferrucci, P. F.; Guidoboni, M.; Rutkowski, P.; Ferraresi, V.; Arance, A.; Guida, M.; Maiello, E.; Gogas, H.; Richtig, E.; Fierro, M. T.; Lebbe, C.; Helgadottir, H.; Queirolo, P.; Spagnolo, F.; Tucci, M.; Del Vecchio, M.; Cao, M. G.; Minisini, A. M.; De Placido, S.; Fernández de Sanmamed Gutiérrez, Miguel; Mallardo, D.; Curvietto, M.; Melero Bermejo, Ignacio; Palmieri, G.; Grimaldi, A. M.; Giannarelli, D.; Dummer, R.; Sileni, V. C.
ISSN: 0732-183X
Volumen: 41
Número: 2
Páginas: 212 - 221
Fecha de publicación: 2023
PURPOSE Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for BRAFV600-mutant metastatic melanoma.METHODS SECOMBIT is a randomized, three-arm, noncomparative phase II trial ( identifier: NCT02631447). Patients with untreated, metastatic BRAFV600-mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -> ipilimumab plus nivolumab [ipilimumab 3 mg/kg once every 3 weeks and nivolumab 1 mg/kg once every 3 weeks x four cycles -> nivolumab 3 mg/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication.RESULTS A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of # 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged.CONCLUSION Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with BRAFV600-mutant melanoma.