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

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.

Informations de copyright

© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: DZ reports institutional grants from Genentech, AstraZeneca, and Plexxikon, as well as personal fees from Genentech, AstraZeneca, Xencor, Memgen, Takeda, Synthekine, Immunos, and Calidi Biotherapeutics, outside of the submitted work. DZ is also an inventor on a patent related to the use of oncolytic Newcastle Disease Virus for cancer therapy. He is also a member of the Parker Institute for Cancer Immunotherapy at MSK. BW reports ad hoc membership of the Scientific Advisory Board of Repare Therapeutics. YLL reports research funding from AstraZeneca, GlaxoSmithKline, and REPARE therapeutics, outside of the submitted work. CFF reports institutional funding from Merck, Daiichi, Genentech/Roche, AstraZeneca, and Bristol-Myers Squibb; personal consulting fees from Seagen and Bristol-Myers Squibb; and Scientific Advisory Board participation for Merck and Genentech (compensation waived), outside of the submitted work. The remaining authors have no disclosures.