J Gynecol Oncol.  2024 Sep;35(5):e69. 10.3802/jgo.2024.35.e69.

Comprehensive characterization of genomic features and clinical outcomes following targeted therapy and secondary cytoreductive surgery in OCCC: a single center experience

• Wijaya ST
• Ngoi NY
• Loh JW
• Tan TZ
• Lim D
• Khan IS
• Thian YL
• Lai A
• Ang BW
• Tong P
• Ng J
• Low JJ
• Ilancheran A
• Lim SE
• Lim YW
• Tan DS

• KMID: 2564955
• DOI: http://doi.org/10.3802/jgo.2024.35.e69

Abstract

Objective
Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS).
Methods
We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available.
Results
64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage. Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%.
Conclusion
Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Keyword

Immunotherapy; Bevacizumab; Ovarian Neoplasms; Adenocarcinoma, Clear Cell; Cytoreduction Surgical Procedures