Treatment of ovarian clear cell carcinoma with immune checkpoint blockade: a case series

Tiffany Y. Sia, Beryl Manning-Geist, Sushmita Gordhandas, Rajmohan Murali, Antonio Marra, Ying L. Liu, Claire F. Friedman, Travis J. Hollmann, Oliver Zivanovic, Dennis S. Chi, Britta Weigelt, Jason A. Konner, Dmitriy Zamarin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background Although immune checkpoint blockade has demonstrated limited effectiveness against ovarian cancer, subset analyses from completed trials suggest possible superior efficacy in the clear cell carcinoma subtype. Objective To describe the outcomes of patients with ovarian clear cell carcinoma treated with immune checkpoint blockade. Methods This was a single-institution, retrospective case series of patients with ovarian clear cell carcinoma treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with or without concomitant cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition between January 2016 and June 2021. Demographic variables, tumor microenvironment, molecular data, and clinical outcomes were examined. Time to treatment failure was defined as the number of days between start of treatment and next line of treatment or death. Results A total of 16 eligible patients were analyzed. The median treatment duration was 56 days (range 14-574); median time to treatment failure was 99 days (range 27-1568). The reason for discontinuation was disease progression in 88% of cases. Four patients (25%) experienced durable clinical benefit (time to treatment failure ≥180 days). One patient was treated twice with combined immune checkpoint blockade and experienced a complete response each time. All 12 patients who underwent clinical tumor-normal molecular profiling had microsatellite-stable disease, and all but one had low tumor mutation burden. Multiplex immunofluorescence analysis available from pre-treatment biopsies of two patients with clinical benefit demonstrated abundant tumor-infiltrating lymphocytes expressing PD-1. Conclusion Our study suggests a potential role for immune checkpoint blockade in patients with clear cell carcinoma of the ovary. Identification of genetic and microenvironmental biomarkers predictive of response will be key to guide therapy.

Original languageEnglish
Pages (from-to)1017-1024
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume32
Issue number8
DOIs
StatePublished - 11 May 2022
Externally publishedYes

Keywords

  • Ovarian Cancer
  • Ovarian Neoplasms

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