{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:30:59Z","timestamp":1789086659488,"version":"build-2803163510"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Prospective and between trial comparisons indicate that first-line treatment with immune checkpoint inhibitors improves survival outcomes compared to first-line therapy with combined BRAF and MEK inhibitors in metastatic melanoma containing BRAFV600E\/K mutations. Long-term outcomes for BRAF\/MEK inhibition after progression on immunotherapy have not been reported. Moreover, clinical variables associated with outcome from treatment with combined BRAF\/MEK inhibition were previously identified in the first-line setting but have not been investigated when targeted therapies are administered after progression on immune therapy. We performed a retrospective single institution analysis of 40 metastatic melanoma patients receiving combined BRAF\/MEK inhibitors after progression on an anti-PD-1 or ipilimumab plus nivolumab to assess response rate by RECIST 1.1, progression-free and overall survival (PFS and OS). Pretreatment clinical variables were analyzed for association with OS. Ipilimumab\/nivolumab was the first-line immunotherapy regimen in 39 patients (97.5%), and BRAFV600E\/K mutations were present in 33 (83%) and 7 (17%) patients, respectively. The median OS from start of BRAF\/MEK inhibitors was 20.3 months (1.73-106.4+, 95% CI of median 13.3-30.7). Clinical characteristics associated with worse survival prior to starting BRAF\/MEK inhibitors included age\u2005&amp;gt;\u200560 years (median OS 14 vs. 28 months; HR 2.5; 95% CI 0.91-6.87, P\u2005=\u2005.023), ECOG-PS\u2005&amp;gt;\u20052 (median OS 7 vs. 33 months; HR 2.89; 95% CI 0.78-10.76, P\u2005=\u2005.018), and presence of bone metastases (median OS 9 vs. 52 months; HR 3.17; 95% CI 1.33-7.54, P\u2005=\u2005.002). These associations with shorter survival maintained their significance on multivariate analysis. If confirmed in larger cohorts, the identified prognostic variables can be used for stratification of patients in future randomized trials.<\/jats:p>","DOI":"10.1093\/oncolo\/oyad300","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T16:32:46Z","timestamp":1700152366000},"page":"e507-e513","source":"Crossref","is-referenced-by-count":7,"title":["Clinical Predictors of Survival in Patients With BRAFV600-Mutated Metastatic Melanoma Treated With Combined BRAF and MEK Inhibitors After Immune Checkpoint Inhibitors"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5306-0571","authenticated-orcid":false,"given":"Adriana M","family":"Kahn","sequence":"first","affiliation":[{"name":"Section of Medical Oncology, Yale School of Medicine , New Haven, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis J","family":"Perry","sequence":"additional","affiliation":[{"name":"Section of Medical Oncology, Yale School of Medicine , New Haven, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Etts","sequence":"additional","affiliation":[{"name":"Section of Medical Oncology, Yale School of Medicine , New Haven, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Kluger","sequence":"additional","affiliation":[{"name":"Section of Medical Oncology, Yale School of Medicine , New Haven, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-9662","authenticated-orcid":false,"given":"Mario","family":"Sznol","sequence":"additional","affiliation":[{"name":"Section of Medical Oncology, Yale School of Medicine , New Haven, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"2024041017253978400_CIT0001","first-page":"1239","article-title":"Pembrolizumab versus 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staging system in the tnm classification","volume-title":"Jpn J Clin Oncol","author":"Ogata","year":"2021"},{"key":"2024041017253978400_CIT0017","first-page":"1382","article-title":"Modeled prognostic subgroups for survival and treatment outcomes in BRAF v600-mutated metastatic melanoma: pooled analysis of 4 randomized clinical trials","volume-title":"JAMA Oncol","author":"Hauschild","year":"2018"},{"key":"2024041017253978400_CIT0018","first-page":"1743","article-title":"Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials","volume-title":"Lancet Oncol","author":"Long","year":"2016"},{"key":"2024041017253978400_CIT0019","first-page":"S122","article-title":"Impact of baseline serum lactate dehydrogenase concentration on the efficacy of pembrolizumab and ipilimumab in patients with advanced melanoma: data from keynote-006","volume-title":"Eur J Cancer","author":"Long","year":"2017"},{"key":"2024041017253978400_CIT0020","first-page":"45","article-title":"Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials","volume-title":"Eur J Cancer","author":"Schadendorf","year":"2017"},{"key":"2024041017253978400_CIT0021","first-page":"294","article-title":"Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib \u00b1 cobimetinib: a pooled analysis of four clinical trials","volume-title":"J Transl Med","author":"Ascierto","year":"2020"},{"key":"2024041017253978400_CIT0022","first-page":"326","article-title":"Vemurafenib in BRAF-mutant metastatic melanoma patients in real-world clinical practice: prognostic factors associated with clinical outcomes","volume-title":"Melanoma 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