Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer

BackgroundTreatment options for advanced thyroid cancer refractory to standard therapies are limited. The safety and efficacy of pembrolizumab were evaluated in patients with advanced differentiated thyroid cancer expressing programmed death ligand 1 (PD-L1).MethodsPatients with advanced thyroid cancer were enrolled in the nonrandomized, phase Ib KEYNOTE-028 trial conducted to evaluate safety and antitumor activity of the anti-programmed death 1 (PD-1) antibody pembrolizumab in advanced solid tumors. Key eligibility criteria were advanced papillary or follicular thyroid cancer, failure of standard therapy, and PD-L1 expression in tumor or stroma cells (assessed by immunohistochemistry). Pembrolizumab 10mg/kg was administered every 2weeks up to 24months or until confirmed progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1.ResultsTwenty-two patients were enrolled: median age was 61years; 59% were women; and 68% had papillary carcinoma. Median follow-up was 31months (range, 7-34months). Treatment-related adverse events were observed in 18 (82%) patients; those occurring in 15% of patients were diarrhea (n=7) and fatigue (n=4). One grade3 treatment-related adverse event occurred (colitis, grade 3); no treatment-related discontinuations or deaths occurred. Two patients had confirmed partial response, for an ORR of 9% (95% confidence interval [CI], 1-29%); response duration was 8 and 20months. Median progression-free survival was 7months (95% CI, 2-14months); median overall survival was not reached (95% CI, 22months to not reached).ConclusionsResults of this phase Ib proof-of-concept study suggest that pembrolizumab has a manageable safety profile and demonstrate evidence of antitumor activity in advanced differentiated thyroid cancer in a minority of patients treated. Further analyses are necessary to confirm these findings.Trial registrationClinicaltrials.gov identifier: NCT02054806. Registered 4 February 2014.