Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE‐158 study

Abstract Background The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE‐158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers. Methods Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review. Results A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9–54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%–13.5%), and median duration of response was 18.4 (range, 4.2‒47.2+) months. ORR was 8.7% (95% CI, 2.4%‒20.8%) among patients with programmed cell death ligand 1 (PD‐L1) combined positive score (CPS) ≥1 ( n = 46) and 5.7% (95% CI, 1.2%‒15.7%) among patients with PD‐L1 CPS <1 ( n = 53). Median overall survival and progression‐free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9‒6.2) months, respectively. Treatment‐related adverse events occurred in 69.9% of patients (grade 3‒5, 14.6%). Conclusions Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD‐L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker‐driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.