Adding an Immune Checkpoint Inhibitor to BRAF/MEK Inhibitors for BRAF V600E-Mutated Anaplastic Thyroid Cancer

Anaplastic thyroid carcinoma is notorious for its aggressiveness, with the BRAF V600E mutation driving approximately 40% of cases. The FDA has approved the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib (DT) for patients with this disease. Despite the combination's overall response rate (ORR) of 69%, updated analyses reveal an ORR of 56% and a median overall survival (OS) of 14.5 months (Nature Med 2023: 29:1103), indicating limited long-term benefits. To investigate whether adding an immune checkpoint inhibitor enhances the durability of response, researchers retrospectively examined the effect of pembrolizumab.

In the dataset, 23 patients with anaplastic thyroid carcinoma were treated with DT, and 48 received DT combined with pembrolizumab (DTP). Median OS was significantly longer in the DTP group than in the DT group (17 months vs. 9 months), although the ORR was similar in the groups (64.5% and 73.3%, respectively). In the DTP group, 14 patients received pembrolizumab upon progression, and 34 received upfront DTP, but median OS did not differ between these patient subgroups (16 and 17 months, respectively). In a separate group of 23 patients, presurgical DTP was linked to a 50% pathological complete response rate and a median OS of 63 months. Safety profiles were acceptable, with immune-related adverse events observed in 32% of patients, none of which were grade 5.