794P - Efficacy of gemcitabine (gem) based therapy in ovarian clear cell carcinoma (OCCC)

Background

OCCC, compared to other histologies, are less responsive to platinum based chemotherapy and suffer a worse prognosis. ARID1A mutations (mt) are the most common mt in OCCC. ARID1A loss has been described to increase replication stress in various tumor models. Anti-metabolites like gem are effective in ARID1A-mt in-vitro.

Methods

We performed a retrospective analysis of the molecular features and treatment outcomes of advanced or relapsed OCCC pts treated at our institution between January 2000 to May 2022. Treatment response was assessed per RECIST1.1. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available (n=60). We hypothesize that gem is more effective than non-gem therapies, especially in ARID1A-mt.

Results

Of 90 advanced or relapsed OCCC patients (pts), median age was 53 years, with median 1 prior line of treatment received. 67 (74.4%) received 2 or more lines, of whom 35 (52.2%) included gem based therapy, mostly in 2^nd line (19/35). 12 pts received platinum-gem with bevacizumab (bev), 18 pts received platinum-gem, 5 received gem monotherapy. 30/60 (50%) were ARID1A-mt. Across all treatment lines, the disease control rate (DCR) to gem was 61.1%. In 2^nd line, DCR was significantly better for gem over non gem (Odds Ratio (OR) OR 6.5, p=0.004), seemingly more for ARID1A-mt (OR of mt VS wild-type (wt) 28 VS 4.2). Early use of gem (2^nd against later lines) and incorporation of bev significantly improved DCR on multivariate analysis (Early use OR 4.1, p: 0.04; Bev OR 7.2, p: 0.02). There was a trend to improved median progression-free survival (mPFS) of 2L gem against non-gem based therapy (7.2 versus 3.2 months(m); Hazard Ratio (HR): 3.48, p = 0.06). This was significant in ARID1A mts (gem VS non-gem: 295 VS 70 days; HR: 4.3, p=0.04) but not in ARID1A-wt (p=0.14). Overall survival was not statistically significant in this study.

Conclusions

This is the largest study of OCCC pts receiving gem based therapy. We show that gemcitabine improved DCR for all OCCC patients, and mPFS in ARID1A-mt especially when used earlier. To maximise gem efficacy, earlier treatment combined with bevacizumab should be considered in OCCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.Y.L. Ngoi: Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, ASGO, JSGO; Financial Interests, Institutional, Advisory Board: Merck/Pfizer, AstraZeneca. F. Blanc-Durand: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Member of Board of Directors: Cureety; Financial Interests, Institutional, Research Grant: AZ; Other, Travel: GSK. D.S. Tan: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Merck Serono, Roche, Eisai, GSK, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, MSD, Eisai, Roche, Genmab, GSK, Boehringer Ingelheim; Financial Interests, Personal, Stocks/Shares: Asian Microbiome Library (AMiLi); Financial Interests, Institutional, Research Grant: Roche, Bayer, Karyopharm Therapeutics, AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Bergen Bio; Financial Interests, Institutional, Local PI: Zeria Pharmaceutical Co., Ltd., Bayer, Byondis B.V.; Non-Financial Interests, Leadership Role, Ex society president: Gynecologic Cancer Group Singapore; Non-Financial Interests, Member of Board of Directors: Gynaecologic Cancer Intergroup (GCIG); Non-Financial Interests, Leadership Role, Ex- Chair: Asia-Pacific Gynecologic Oncology Trials Group (APGOT); Non-Financial Interests, Institutional, Product Samples, Research Study: MSD, Eisai, AstraZeneca. All other authors have declared no conflicts of interest.