Browse

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

Cited 36 time in Web of Science Cited 38 time in Scopus
Authors
Mehnert, Janice M; Varga, Andrea; Brose, Marcia S.; Aggarwal, Rahul R; Lin, Chia-Chi; Prawira, Amy; de Braud, Filippo; Tamura, Kenji; Doi, Toshihiko; Piha-Paul, Sarina A.; Gilbert, Jill; Saraf, Sanatan; Thanigaimani, Pradeep; Cheng, Jonathan D; Keam, Bhumsuk
Issue Date
2019-03-04
Publisher
BioMed Central
Citation
BMC Cancer. 2019 Mar 04;19(1):196
Keywords
Thyroid cancerImmunotherapyPembrolizumabAnti–PD-1PD-1PD-L1
Abstract
Background
Treatment 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).

Methods
Patients 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.

Results
Twenty-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).

Conclusions
Results 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 registration
Clinicaltrials.gov identifier: NCT02054806. Registered 4 February 2014.
ISSN
1471-2407
Language
English
URI
https://hdl.handle.net/10371/147197
DOI
https://doi.org/10.1186/s12885-019-5380-3
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse