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

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 thyroi...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399859/
https://www.ncbi.nlm.nih.gov/pubmed/30832606
http://dx.doi.org/10.1186/s12885-019-5380-3
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author 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
author_facet 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
author_sort Mehnert, Janice M.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5380-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-63998592019-03-13 Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer 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 BMC Cancer Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5380-3) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-04 /pmc/articles/PMC6399859/ /pubmed/30832606 http://dx.doi.org/10.1186/s12885-019-5380-3 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
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
Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer
title Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer
title_full Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer
title_fullStr Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer
title_full_unstemmed Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer
title_short Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer
title_sort safety and antitumor activity of the anti–pd-1 antibody pembrolizumab in patients with advanced, pd-l1–positive papillary or follicular thyroid cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399859/
https://www.ncbi.nlm.nih.gov/pubmed/30832606
http://dx.doi.org/10.1186/s12885-019-5380-3
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