Abstract 574P
Background
PARPi are indicated as maintenance therapy after 1st line chemotherapy, for patients (pts) with high-grade ovarian cancer (HGOC) in case of BRCA mutation, high genomic instability score (GIS), or objective response to platinum. Herein, GIS is required straight away, for all pts with HGOC to select the best maintenance strategy between bevacizumab, PARPi or both combined. Around 10% of HGOC are platinum-refractory with progressive disease during or within 4 weeks of last platinum, and additional 10% present no objective response (OR-) to platinum, and both are not eligible for PARPi. We aim to evaluate the capacity of GIS to detect pts who did not benefit from platinum and harbor the poorest prognosis.
Methods
This is a retrospective analysis of all pts tested for GIS by myChoice HRD Plus assay. Pts included presented HGOC with FIGO III/IV diseases and treated according to national guidelines. GIS was performed on pretreatment biopsy preferably. If tumor surface was <7mm2 or if GIS test resulted non conclusive, a second attempt was performed on interval surgery samples. Response rate was evaluated according to RECIST1.1.
Results
120 pts were included in this analysis. Median age was 66 years, 94% of pts had high-grade serous carcinoma and 12 BRCA1/2 mutations were detected. 24 patients benefited from frontline complete cytoreductive (CC0) surgery, 63 pts from inteval CC0 surgery, 19 pts with incomplete/no surgery, and the remaining 14 pts are ongoing chemotherapy. Response rate to platinum-based NACT was 88%. Myriad GIS yielded contributive results for 88% of the pts. Among pts with >6 months follow-up (N=87), 32% were GIS positive (score ≥ 42) and 18% were considered resistant to platinum (OR- or refractory). 80% of pts with resistant tumor were GIS negative versus 65% with sensitive tumors, however the difference did not reach statistical significance (P=0.27). Median GIS was 26.5 in the resistant group versus 29.5 in the sensitive group (P=0.32).
Conclusions
GIS at diagnostic on an all comer population could not reliably discriminate platinum-resistant and platinum-sensitive pts, among HGOC pts. Whether patients with discordance between GIS and platinum response may benefit from PARP inhibitors is currently being investigated.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Blanc-Durand: Financial Interests, Institutional, Advisory Role: Eisai; Financial Interests, Personal, Other: GSK; Non-Financial Interests, Institutional, Advisory Role: Astrazeneca; Financial Interests, Personal, Project Lead: Cureety. J. Michels: Financial Interests, Institutional, Advisory Role: GSK. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AstraZeneca, Clovis, Ability Pharma, MSD, Tesaro, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: Tesaro, AstraZeneca, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AstraZeneca; Financial Interests, Institutional, Funding, CI clinical trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer. All other authors have declared no conflicts of interest.