Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Gynecologic oncology 2019-02, Vol.152 (2), p.251-258
Hauptverfasser: Boland, Julia L., Zhou, Qin, Martin, Madhuri, Callahan, Margaret K., Konner, Jason, O'Cearbhaill, Roisin E., Friedman, Claire F., Tew, William, Makker, Vicky, Grisham, Rachel N., Hensley, Martee L., Zecca, Nicholas, Iasonos, Alexia E., Snyder, Alexandra, Hyman, David M., Sabbatini, Paul, Aghajanian, Carol, Cadoo, Karen A., Zamarin, Dmitriy
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. •In ovarian cancer patients treated with immune checkpoint blockade, early discontinuation of therapy is common.•Symptomatic disease progression was common and accounted for early treatment discontinuation in the majority of patients.•Ovarian cancer patients with heavily pretreated, recurrent disease may not be suitable candidates for immunotherapy.•Pre-treatment clinical parameters can identify the patients at risk for early discontinuation and symptomatic progression.
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2018.11.025