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


Authors: Boland, J. L.; Zhou, Q.; Martin, M.; Callahan, M. K.; Konner, J.; O'Cearbhaill, R. E.; Friedman, C. F.; Tew, W.; Makker, V.; Grisham, R. N.; Hensley, M. L.; Zecca, N.; Iasonos, A. E.; Snyder, A.; Hyman, D. M.; Sabbatini, P.; Aghajanian, C.; Cadoo, K. A.; Zamarin, D.
Article Title: Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade
Abstract: Objective: 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. Methods: 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. Results: 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. Conclusions: 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. © 2018 The Authors
Keywords: adult; aged; gene mutation; major clinical study; advanced cancer; drug withdrawal; ovarian cancer; cancer immunotherapy; retrospective study; tumor suppressor gene; liver metastasis; immunotherapy; ovary carcinoma; hospital patient; multivariate logistic regression analysis; immunomodulating agent; ctla-4; immunosuppressive treatment; liver parenchyma; univariate analysis; disease exacerbation; treatment withdrawal; pd-1; peritoneal disease; human; female; priority journal; article; neutrophil lymphocyte ratio; gilvetmab
Journal Title: Gynecologic Oncology
Volume: 152
Issue: 2
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2019-02-01
Start Page: 251
End Page: 258
Language: English
DOI: 10.1016/j.ygyno.2018.11.025
PUBMED: 30470581
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Vicky Makker
    74 Makker
  2. Jason Konner
    85 Konner
  3. Dmitriy Zamarin
    56 Zamarin
  4. Paul J Sabbatini
    201 Sabbatini
  5. Qin Zhou
    120 Zhou
  6. Alexia Elia Iasonos
    179 Iasonos
  7. Rachel Nicole Grisham
    35 Grisham
  8. Martee L Hensley
    220 Hensley
  9. David Hyman
    187 Hyman
  10. Margaret Kathleen Callahan
    103 Callahan
  11. William P Tew
    122 Tew
  12. Karen Anne Cadoo
    27 Cadoo
  13. Madhuri Martin
    3 Martin
  14. Julia Lindsay Boland
    1 Boland
  15. Nicholas Anthony Zecca
    1 Zecca