Anti-PD-L1 plus targeted therapy in anaplastic thyroid carcinoma

A phase 2 nonrandomized clinical trial, recently published on JAMA Oncology, shows promising results with the anti-PD-L1 atezolizumab combined with genetically matched targeted therapy in patients with anaplastic thyroid carcinoma, with or without BRAF mutations.

Authors enrolled 42 patients in three different targeted therapy cohorts: patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2); patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). The median overall survival across the three cohorts was 19 months, ranging from 43 months in patients from cohort 1 to 6.21 months in cohort 3; the progression-free survival was of 13.9 months in cohort1, 4.8 months in cohort 2 and 1.3 months in cohort 3. «Primary resistance to single-agent targeted therapy is common in anaplastic thyroid carcinoma and despite success with BRAF and MEK inhibitors, specifically for BRAF mutations, inevitably resistance occurs. Recognizing that these tumors have oncogenic driver mutations, but that invariably develop resistance to targeted therapy alone, we designed this novel trial combining atezolizumab with targeted therapy, hypothesizing that this approach would result in a significantly longer median overall survival», authors say. «Results show that the genetically-matched targeted therapy plus immunotherapy combination strategy across cohorts 1 to 3 resulted in an overall survival of 19 months—to our knowledge the longest overall survival reported to date in an anaplastic thyroid carcinoma clinical trial. Mutation-directed targeted therapy in combination with PD-L1 inhibitor immunotherapy is a promising strategy to extend overall survival in patients with anaplastic thyroid carcinoma. Further studies in patients with non–BRAF-mutated anaplastic thyroid carcinoma, using better targeted agents, are needed», authors conclude.