Publicaciones científicas
Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma
Paolo A Ascierto 1 , Mario Mandalà 2 3 , Pier Francesco Ferrucci 4 , Massimo Guidoboni 5 , Piotr Rutkowski 6 , Virginia Ferraresi 7 , Ana Arance 8 , Michele Guida 9 , Evaristo Maiello 10 , Helen Gogas 11 , Erika Richtig 12 , Pietro Quaglino 13 , Céleste Lebbé 14 , Hildur Helgadottir 15 , Paola Queirolo 16 17 , Francesco Spagnolo 16 18 , Marco Tucci 19 , Michele Del Vecchio 20 , Maria Gonzalez-Cao 21 , Alessandro Marco Minisini 22 , Sabino De Placido 23 , Miguel F Sanmamed 24 , Milena Casula 25 , Jenny Bulgarelli 5 , Marina Pisano 25 , Claudia Piccinini 5 , Luisa Piccin 26 , Antonio Cossu 27 , Domenico Mallardo 1 , Miriam Paone 1 , Maria Grazia Vitale 1 , Ignacio Melero 24 , Antonio M Grimaldi 1 28 , Diana Giannarelli 29 , Giuseppe Palmieri 25 , Reinhard Dummer 30 , Vanna Chiarion Sileni 26
Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable BRAFV600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.
Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).
Results: Brain metastases were discovered during the trial in 23/69 patients in arm A, 11/69 in arm B, and 9/68 in arm C. At a median follow-up of 56 months, the 60-month brain metastases-free survival rates were 56% for arm A, 80% for arm B (hazard ratio [HR] vs. A: 0.40, 95% confidence interval [CI] 0.23 to 0.58), and 85% for arm C (HR vs. A: 0.35, 95% CI 0.16 to 0.76).
Conclusions: In patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new brain metastases-free survival than the reverse sequence. A regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to be protective against brain metastases. (ClinicalTrials.gov number NCT02631447.).
CITA DEL ARTÍCULO NEJM Evid. 2024 Oct;3(10):EVIDoa2400087. doi: 10.1056/EVIDoa2400087. Epub 2024 Sep 24
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