Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade.
Adult
Aged
Antineoplastic Agents, Immunological
/ administration & dosage
B7-H1 Antigen
/ antagonists & inhibitors
CTLA-4 Antigen
/ antagonists & inhibitors
Carcinoma, Ovarian Epithelial
/ drug therapy
Disease Progression
Fallopian Tube Neoplasms
/ drug therapy
Female
Humans
Immunotherapy
/ methods
Middle Aged
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Retrospective Studies
Young Adult
CTLA-4
Immunotherapy
Ovarian cancer
PD-1
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
27
09
2018
revised:
12
11
2018
accepted:
15
11
2018
pubmed:
25
11
2018
medline:
23
2
2019
entrez:
25
11
2018
Statut:
ppublish
Résumé
Delayed responses observed with immune checkpoint blockade (ICB) present a challenge for patients with peritoneal malignancies, who risk early symptomatic disease progression requiring treatment discontinuation. While efforts are ongoing to define the biomarkers of response, it is equally important to identify patients at risk for early discontinuation. We sought to investigate the timing of disease progression in epithelial ovarian cancer (EOC) patients treated with ICB and to identify pre-treatment clinical parameters associated with early discontinuation. Retrospective analysis was performed on EOC patients treated with ICB at MSKCC from January 2013 to May 2017. Cutoffs for early and very early discontinuation due to disease progression were defined at 12 and 8 weeks, respectively. Univariate and multivariate logistic regression models were built based on pre-treatment clinical variables. Of 108 identified patients, 89 were included in the analysis. Forty-six (51.7%) patients discontinued therapy early, 30 of which (33.7%) discontinued therapy very early. Eight patients (9.0%) died within 12 weeks of ICB initiation from disease progression. In multivariate analyses, bulky peritoneal disease (p = 0.009, OR: 4.94) and liver parenchymal metastases (p = 0.001, OR: 8.08) were associated with early discontinuation. Liver parenchymal metastases (p = 0.001, OR 6.64), and high neutrophil-to-lymphocyte ratio (p = 0.021, OR: 3.54), were associated with very early discontinuation. Over 50% of EOC patients suffer disease progression requiring early discontinuation of ICB. Pre-treatment prognostic clinical characteristics may identify patients at highest risk for early discontinuation due to disease progression and warrant caution in using these agents in late line patients with advanced disease.
Identifiants
pubmed: 30470581
pii: S0090-8258(18)31445-8
doi: 10.1016/j.ygyno.2018.11.025
pmc: PMC6613945
mid: NIHMS1038741
pii:
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
CD274 protein, human
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
251-258Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA020449
Pays : United States
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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