Abstract
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 10 mg/kg was administered every 2 weeks up to 24 months 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 61 years; 59% were women; and 68% had papillary carcinoma. Median follow-up was 31 months (range, 7–34 months). 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 grade ≥ 3 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 20 months. Median progression-free survival was 7 months (95% CI, 2–14 months); median overall survival was not reached (95% CI, 22 months 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.
Highlights
Treatment options for advanced thyroid cancer refractory to standard therapies are limited
Lenvatinib was associated with significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared with placebo; median overall survival (OS) was not reached after a median follow-up of 17 months
Study design and patients Eligibility criteria were age ≥ 18 years; presence of cytologically or histologically confirmed, programmed death ligand 1 (PD-L1)–positive, locally advanced or metastatic follicular or papillary thyroid cancer in which, per the opinion of the treating physician, previous standard therapy was ineffective, did not occur, or was not considered appropriate; measurable disease based on Response Evaluation Criteria In Solid Tumors, version 1.1 (RECIST v1.1); Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; and adequate organ function
Summary
Treatment options for advanced thyroid cancer refractory to standard therapies are limited. The prognosis for most thyroid cancers is generally good (98% overall 5-year survival rate) [2], approximately 10% of patients with differentiated thyroid cancer develop progressive invasive primary disease, 5% develop distant metastases, and 20–30% experience disease recurrence [3]. Results of a phase III randomized trial revealed a progression-free survival (PFS) benefit with sorafenib compared with placebo in patients with RAI-refractory, advanced, differentiated thyroid cancer [10]. Lenvatinib was associated with significant improvement in PFS and objective response rate (ORR) compared with placebo; median overall survival (OS) was not reached after a median follow-up of 17 months. Sorafenib and lenvatinib are recommended by the National Comprehensive Cancer Network for the treatment of progressive, RAI-refractory differentiated thyroid carcinoma [4].
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