Pembrolizumab + dabrafenib/trametinib drives 97% R0/R1 resections and 20-mo OS in BRAF V600E anaplastic thyroid cancer

Neoadjuvant BRAF inhibitor DTP, the combination of dabrafenib (150 mg BID) + trametinib (2 mg QD) for 3-6 weeks followed by pembrolizumab 200 mg Q3W—was tested in a multicenter phase 2 trial (NCT04675710) enrolling 42 stage IVB/IVC BRAF V600E-mutated ATC patients; 36 were evaluable. After a median 4 cycles, 72% achieved radiographic PR/CR and 30/36 (83%) proceeded to surgery, with 29/30 (97%) attaining R0/R1 margins and 20/30 (67%) showing complete pathologic response. Median PFS hit 13.9 mo and median OS 20 mo (1- and 2-yr OS = 71%/48%), markedly exceeding the ROAR dabrafenib + trametinib benchmarks of 6.7 mo PFS and 13.5 mo OS. Grade ≥3 toxicities were uncommon except for eight grade 5 events (22%), only two deemed possibly/probably related to therapy.