{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:06:31Z","timestamp":1793405191605,"version":"4.5.0"},"reference-count":48,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol Myers Squibb, Inc.","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["bmjonc"],"accepted":{"date-parts":[[2025,11,17]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Dual immuno-oncology (IO) therapy or BRAF\/MEK inhibitor combinations are approved first-line (1L) treatment options for\n                      <jats:italic>BRAF-<\/jats:italic>\n                      mutant advanced melanoma. In the absence of head-to-head trials comparing 1L nivolumab plus relatlimab (NIVO+RELA) to BRAF\/MEK inhibitors, we compared its efficacy to dabrafenib+trametinib (DAB+TRAM), encorafenib+binimetinib (ENCO+BINI), vemurafenib+cobimetinib (VEM+COBI) and atezolizumab (ATEZO)+VEM+COBI using matching-adjusted indirect comparisons (MAICs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patient-level data for NIVO+RELA from the RELATIVITY-047 trial (\n                      <jats:italic>BRAF<\/jats:italic>\n                      -mutant subset) and aggregate data from the COMBI-d\/v, COLUMBUS, coBRIM and IMspire150 trials were used. Adults with untreated\n                      <jats:italic>BRAF-<\/jats:italic>\n                      mutant advanced melanoma receiving 1L therapy were included. Separate unanchored MAICs were conducted to compare outcomes between NIVO+RELA\u2009versus comparators. MAICs matched on baseline characteristics per data availability and clinical relevance (age, sex, metastatic stage, prior IO, brain metastases, tumour size, etc.). Overall survival (OS) and investigator-assessed progression-free survival (PFS) were compared using weighted Cox proportional hazards models and, due to violation of the proportional hazards assumption, interval Cox models with boundaries at 12 (doublets) or 24 (ATEZO+VEM+COBI) months from treatment initiation. Investigator-assessed overall response rate (ORR) and safety outcomes (any adverse event (AE), grade 3\/4 AEs, AEs leading to discontinuation, specific AEs) were compared via ORs and risk differences (RDs), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BRAF<\/jats:italic>\n                      -mutant patients from RELATIVITY-047 (n=136) were matched to patients who received DAB+TRAM (n=563), ENCO+BINI (n=192), VEM+COBI (n=247) or ATEZO+VEM+COBI (n=256). Post-matching, NIVO+RELA was associated with longer OS after 12 months versus DAB+TRAM (HR (95% CI) 0.47 (0.31 to 0.70)), ENCO+BINI (0.51 (0.32 to 0.83)) and VEM+COBI (0.41 (0.26 to 0.62)) and at any time versus ATEZO+VEM+COBI (0.68 (0.48\u20130.98)). PFS was shorter versus DAB+TRAM (1.36 (0.96 to 1.94)), ENCO+BINI (1.72 (1.13 to 2.61)) and VEM+COBI (1.27 (0.89 to 1.81)) in the first 12 months but favoured NIVO+RELA after 12 months (0.56 (0.33 to 0.93), 0.63 (0.28 to 1.45) and 0.41 (0.24 to 0.70)). PFS was similar versus ATEZO+VEM+COBI through 24 months (1.21 (0.87 to 1.68)) and favoured NIVO+RELA beyond 24 months (0.45 (0.19 to 1.07)). ORR was lower with NIVO+RELA\u2009versus all comparators. Grade 3\/4 AEs were less frequent with NIVO+RELA\u2009versus DAB+TRAM (RD (95% CI) \u221220.1% (\u221230.6 to \u22129.5)), ENCO+BINI (\u221229.2% (-42.2 to \u221216.3)), VEM+COBI (\u221236.9% (\u221247.5 to \u221226.3)) and ATEZO+VEM+COBI (percentage: 40.0% vs 74.9%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These MAICs suggest that 1L dual IO therapy with NIVO+RELA confers a long-term OS advantage in\n                      <jats:italic>BRAF<\/jats:italic>\n                      -mutant advanced melanoma compared with BRAF\/MEK inhibitor combinations despite lower ORR, consistent with prior evidence for 1L NIVO+IPI in this setting. As unanchored analyses, potential residual confounding remains, and results should be interpreted cautiously.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjonc-2025-000912","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T07:20:20Z","timestamp":1765783220000},"page":"e000912","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of nivolumab plus relatlimab versus BRAF\/MEK inhibitors for first-line treatment of\n                    <i>BRAF<\/i>\n                    -mutant advanced melanoma: A matching-adjusted indirect comparison"],"prefix":"10.1136","volume":"4","clinical-trial-number":[{"clinical-trial-number":"nct03470922","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01584648","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01597908","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01909453","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01689519","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02908672","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9736-9119","authenticated-orcid":false,"given":"David M","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA"},{"name":"Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-1193","authenticated-orcid":false,"given":"James W","family":"Smithy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennell","family":"Palaia","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Patel","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"D\u2019Adamo","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Mattera","sequence":"additional","affiliation":[{"name":"Analysis Group Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Analysis Group Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0835-800X","authenticated-orcid":false,"given":"Viviana","family":"Garcia-Horton","sequence":"additional","affiliation":[{"name":"Analysis Group Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad A","family":"Tarhini","sequence":"additional","affiliation":[{"name":"Departments of Cutaneous Oncology and Immunology, H. 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