{"entity":{"id":"io-first-then-braf-mek","kind":"pairing","name":"Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)","aka":[],"tldr":"In BRAF-mutant melanoma, start with immunotherapy and keep the targeted pills in reserve; the reverse order costs lives.","summary":"This sequence rule for BRAF-mutant melanoma is to start with immune checkpoint inhibitors, nivolumab with ipilimumab, and to keep the BRAF/MEK inhibitors dabrafenib and trametinib, or encorafenib-based therapy, in reserve. Immunotherapy responses are durable and can be curative, whereas BRAF/MEK responses are fast but nearly always temporary, so using the durable option first preserves the fast option as a rescue. The phase 3 DREAMseq trial showed a clear overall survival advantage for immunotherapy first, and the phase 2 SECOMBIT trial was concordant. Targeted therapy still works after immunotherapy, but immunotherapy after targeted therapy underperforms, possibly because progression on BRAF/MEK inhibitors is rapid and the tumours are immunologically cold.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02224781: DREAMseq (ECOG-ACRIN EA6134)","url":"https://clinicaltrials.gov/study/NCT02224781"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":["braf"],"drugs":["nivolumab","ipilimumab","dabrafenib-trametinib","encorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dreamseq"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"checkpoint-inhibitor","b":"dabrafenib-trametinib","rationale":"Immunotherapy responses are durable and can be curative; BRAF/MEK responses are fast but nearly always temporary. Using the durable option first preserves the fast option as a rescue.","evidence":"Phase 3 DREAMseq; phase 2 SECOMBIT concordant.","pairingType":"sequence"},"route":"/pairings/io-first-then-braf-mek/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"drug":[{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"trial":[{"id":"dreamseq","kind":"trial","name":"DREAMseq (ECOG-ACRIN EA6134)","route":"/trials/dreamseq/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}}