{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:26:44Z","timestamp":1793114804832,"version":"4.5.0"},"reference-count":39,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Sydney Medical Foundation"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,6,9]]},"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patients with V600BRAF mutant metastatic melanoma have higher rates of progression-free survival (PFS) and overall survival (OS) with first-line anti-PD1 (PD1]+anti-CTLA-4 (IPI) versus PD1. Whether this is also true after BRAF\/MEKi therapy is unknown. We aimed to determine the efficacy and safety of PD1 versus IPI +PD1 after BRAF\/MEK inhibitors (BRAF\/MEKi).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with V600BRAF mutant metastatic melanoma treated with BRAF\/MEKi who had subsequent PD1 versus IPI+PD1 at eight centers were included. The endpoints were objective response rate (ORR), PFS, OS and safety in each group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 200 patients with V600E (75%) or non-V600E (25%) mutant metastatic melanoma treated with BRAF\/MEKi (median time of treatment 7.6 months; treatment cessation due to progressive disease in 77%), 115 (57.5%) had subsequent PD1 and 85 (42.5%) had IPI+PD1. Differences in patient characteristics between PD1 and IPI+PD1 groups included, age (med. 63 vs 54 years), time between BRAF\/MEKi and PD1\u00b1IPI (16 vs 4\u2009days), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of \u22651 (62% vs 44%), AJCC M1C\/M1D stage (72% vs 94%) and progressing brain metastases at the start of PD1\u00b1IPI (34% vs 57%). Median follow-up from PD1\u00b1IPI start was 37.8 months (95% CI, 33.9 to 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p=0.5713). Median PFS was 3.4 months; 3.4 with PD1 vs 3.6 months with IPI+PD1 (p=0.6951). Median OS was 15.4 months; 14.4 for PD1 vs 20.5 months with IPI+PD1 (p=0.2603). The rate of grade 3 or 4 toxicities was higher with IPI+PD1 (31%) vs PD1 (7%). ORR, PFS and OS were numerically higher with IPI+PD1\u2009vs PD1 across most subgroups except for females, those with &lt;10\u2009days between BRAF\/MEKi and PD1\u00b1IPI, and those with stage III\/M1A\/M1B melanoma. The combination of ECOG PS=0\u2009and absence of liver metastases identified patients with &gt;3 years OS (area under the curve, AUC=0.74), while ECOG PS \u22651, progressing brain metastases and presence of bone metastases predicted primary progression (AUC=0.67).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IPI+PD1\u2009and PD1 after BRAF\/MEKi have similar outcomes despite worse baseline prognostic features in the IPI+PD1 group, however, IPI+PD1 is more toxic. A combination of clinical factors can identify long-term survivors, but less accurately those with primary resistance to immunotherapy after targeted therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-004610","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T12:15:22Z","timestamp":1657196122000},"page":"e004610","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Efficacy and safety of anti-PD1 monotherapy or in combination with ipilimumab after BRAF\/MEK inhibitors in patients with BRAF mutant metastatic melanoma"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3540-8906","authenticated-orcid":false,"given":"Ines","family":"Pires da Silva","sequence":"first","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo Antonio","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B","family":"Johnson","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Carlino","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, North Sydney, New South Wales, Australia"},{"name":"Blacktown & Westmead Hospital, Sydney, New South Wales, 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