According to a phase 2 study, neoadjuvant pembrolizumab with dabrafenib and trametinib enabled surgical resection among patients with BRAF V600E-mutated anaplastic thyroid cancer as compared to historical controls, leading to improved progression-free survival (PFS) and overall survival (OS).

These data were first presented by Mark Zafereo, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In a retrospective series of patients in this population, Dr Zafereo and coauthors wrote, neoadjuvant pembrolizumab with dabrafenib and trametinib “achieved locoregional control without radical surgery … providing rationale to evaluate the efficacy and safety in a phase 2 trial.”

In this single-arm, multicenter trial, 42 patients with BRAF V600E mutated stage IVB or stage IVC anaplastic thyroid cancer were enrolled across 5 centers in the United States. Patients received a 3- to 6-week run-in of 150 mg dabrafenib twice daily and 2 mg trametinib daily followed by the addition of 200 mg pembrolizumab three times a week. After surgery, patients continued on pembrolizumab or pebrolizumab with dabrafenib plus trametinib and radiotherapy, or transitioned to adjuvant pembrolizumab with dabrafenib plus trametinib for up to 26 cycles. The primary end point was R0/R1 resection rate (compared to the historical record of 5%) and OS. Secondary end points included response following pembrolizumab with dabrafenib plus trametinib and PFS.

Among 36 evaluable patients, 26 achieved radiographic partial response or complete response. After neoadjuvant pembrolizumab with dabrafenib plus trametinib, 83% of patients underwent surgery. Of those patients 97% achieved a R0/R1 resection. Complete anaplastic thyroid cancer pathologic response occurred in 67% of patients, while 33% retained residual anaplastic thyroid cancer in the surgical specimen. The median OS was 20 months with a 1-year OS rate of 71% and 2-year OS rate of 48%. Those patients who achieved a complete pathological response had better 2-year OS than those with residual anaplastic thyroid cancer (69% vs 22%; P = .02). The median PFS was 13.9 months with a 1-year PFS rate of 57% and a 2-year PFS rate of 36%.

There were 8 patients (22%) with a reported grade 5 adverse event, including 1 possible (duodenal perforation), 1 probable (kidney injury with sepsis), and 6 unlikely or unrelated treatment-related deaths. 

Dr Zafereo et al concluded, “This approach should now be considered standard of care” for patients with BRAF V600E-mutated anaplastic thyroid cancer.

Source:

Zafereo M, Wang R, Busaidy N, et al. Neoadjuvant pembrolizumab in combination with dabrafenib and trametinib (DTP) for BRAF V600E-mutated anaplastic thyroid cancer (BRAFm-ATC): A multicenter phase 2 trial. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract #6008