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.).
Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma / Ascierto, Paolo A.; Mandalà, Mario; Ferrucci, Pier Francesco; Guidoboni, Massimo; Rutkowski, Piotr; Ferraresi, Virginia; Arance, Ana; Guida, Michele; Maiello, Evaristo; Gogas, Helen; Richtig, Erika; Quaglino, Pietro; Lebbé, Céleste; Helgadottir, Hildur; Queirolo, Paola; Spagnolo, Francesco; Tucci, Marco; Del Vecchio, Michele; Gonzalez-Cao, Maria; Minisini, Alessandro Marco; De Placido, Sabino; Sanmamed, Miguel F.; Casula, Milena; Bulgarelli, Jenny; Pisano, Marina; Piccinini, Claudia; Piccin, Luisa; Cossu, Antonio; Mallardo, Domenico; Paone, Miriam; Vitale, Maria Grazia; Melero, Ignacio; Grimaldi, Antonio M.; Giannarelli, Diana; Palmieri, Giuseppe; Dummer, Reinhard; Sileni, Vanna Chiarion. - In: NEJM EVIDENCE. - ISSN 2766-5526. - 3:10(2024). [10.1056/evidoa2400087]
Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma
Cossu, Antonio;Palmieri, GiuseppeInvestigation
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2024-01-01
Abstract
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.).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.