Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer.
Adenocarcinoma, Follicular
/ drug therapy
Adult
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
B7-H1 Antigen
/ metabolism
Colitis
/ chemically induced
Diarrhea
/ chemically induced
Fatigue
/ chemically induced
Female
Humans
Male
Middle Aged
Progression-Free Survival
Proof of Concept Study
Response Evaluation Criteria in Solid Tumors
Thyroid Cancer, Papillary
/ drug therapy
Thyroid Neoplasms
/ drug therapy
Treatment Outcome
Young Adult
Anti–PD-1
Immunotherapy
PD-1
PD-L1
Pembrolizumab
Thyroid cancer
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
04 Mar 2019
04 Mar 2019
Historique:
received:
22
01
2018
accepted:
19
02
2019
entrez:
6
3
2019
pubmed:
6
3
2019
medline:
2
7
2019
Statut:
epublish
Résumé
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). 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. 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). 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. Clinicaltrials.gov identifier: NCT02054806 . Registered 4 February 2014.
Sections du résumé
BACKGROUND
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
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
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
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
BACKGROUND
Clinicaltrials.gov identifier: NCT02054806 . Registered 4 February 2014.
Identifiants
pubmed: 30832606
doi: 10.1186/s12885-019-5380-3
pii: 10.1186/s12885-019-5380-3
pmc: PMC6399859
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
CD274 protein, human
0
pembrolizumab
DPT0O3T46P
Banques de données
ClinicalTrials.gov
['NCT02054806']
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
196Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000371
Pays : United States
Références
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12293-7
pubmed: 12218188
Biomed Pharmacother. 2008 Oct;62(8):559-63
pubmed: 18725177
Cancer Immunol Immunother. 2011 Mar;60(3):319-26
pubmed: 21267721
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Ann Oncol. 2012 Oct;23 Suppl 7:vii110-9
pubmed: 22997443
Endocr Relat Cancer. 2013 Feb 18;20(1):103-10
pubmed: 23193072
Cancer Med. 2013 Oct;2(5):662-73
pubmed: 24403232
Lancet. 2014 Jul 26;384(9940):319-28
pubmed: 24768112
N Engl J Med. 2015 Feb 12;372(7):621-30
pubmed: 25671254
Am Health Drug Benefits. 2015 Feb;8(1):30-40
pubmed: 25964831
J Clin Endocrinol Metab. 2016 Jul;101(7):2863-73
pubmed: 27045886
Oncotarget. 2016 May 31;7(22):32318-28
pubmed: 27086918
Lancet Oncol. 2016 Jul;17(7):956-965
pubmed: 27247226
J Clin Oncol. 2016 Nov 10;34(32):3838-3845
pubmed: 27646946
Arch Pathol Lab Med. 2016 Nov;140(11):1259-1266
pubmed: 27788043
Expert Rev Anticancer Ther. 2018 Feb;18(2):149-159
pubmed: 29241377