Abstract 835P
Background
Ovarian clear cell carcinoma (OCCC) is associated with chemotherapy resistance. Limited data are available regarding the efficacy of targeted therapies such as anti-PD1/PDL1 checkpoint inhibitors (CPI) and bevacizumab (Bev) in OCCC. We characterized the molecular features and treatment outcomes of OCCC patients (pts) treated at our institution.
Methods
Retrospective review of medical records and next-generation sequencing (NGS) data, was performed on 157 OCCC pts treated between 2000-2020. Treatment response was assessed by RECIST1.1.
Results
Median age was 54 yrs (range 26-82). 70% pts were Chinese, 12.1% Malay and 7% Indian. At the time of diagnosis, 84(53.5%) had stage I, 17(10.8%) stage II, 42(26.8%) stage III and 13(8.3%) stage IV disease. 127/157(80.9%) pts had optimal debulking. Of 101 stage I-II pts, no difference in relapse-free survival was noted by stage, age, race or chemotherapy on multi-variate analysis. 89/157 pts had advanced/relapsed disease (advOCCC), 22/89(24.7%) pts received Bev, 21/89(23.6%) received CPI and 19/89(21.3%) underwent secondary debulking. An improvement in median progression-free survival (PFS) was noted for advOCCC pts receiving chemotherapy (CTX) + Bev compared to CTX alone in the first-line (17.2 vs 10.5mth, p>0.05), and second-line settings (5.1 vs 3.6mth, p>0.05), respectively. Of 21 pts who received CPI, 17 were evaluable. ORR was 17.6% (3/17) with 3 PR, 3 SD and 11 PD as best response. 2 pts had durable response to pembrolizumab, receiving 29 and 36 cycles of pembrolizumab respectively. 1 durable responder was re-challenged with pembrolizumab plus Bev after PD on pembrolizumab monotherapy, and responded for additional 8mth. NGS on 21 advOCCC tumors revealed common (>20%) mutations in PI3KCA(61.9%), ARID1A(57.1%), TP53(38.1%), KRAS(28.6%) and ERBB3 amplification (23.8%). No mutation in mismatch-repair genes was detected. Median tumor mutational burden was 4 (range 0-11). Mutations in the PI3K/AKT/PTEN/MTOR pathway were associated with worse first-line PFS (Cox regression 1.26, p=0.05).
Conclusions
Encouraging and durable responses were observed following the use of Bev and CPI in advOCCC. Further trials are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NMRC/CSA-INV-0016/2017.
Disclosure
N.Y.L. Ngoi: Honoraria (self): Johnson & Johnson; Travel/Accommodation/Expenses: AstraZeneca. D.S. Tan: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self): Foundation Medicine; Honoraria (self): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self): Tessa Therapeutics; Research grant/Funding (institution): Karyopharm Therapeutics; Travel/Accommodation/Expenses: Novartis. All other authors have declared no conflicts of interest.