Abstract 65P
Background
BRCA 1/2 mutations (BRCAmut) and homologous recombination deficient (HRD) status are well-established prognostic and predictive factors of the magnitude of response to PARPi. CRS is also known as a prognostic value in patients with AEOC undergoing interval debulking surgery after neoadjuvant chemotherapy (NACT). The role of CRS in predicting PARPi response in AEOC is unclear and is the aim of this analysis.
Methods
We conducted a retrospective study of 45 patients diagnosed AEOC, FIGO stage III-IV, treated with platinum-based NACT followed by interval debulking surgery, from April 2018 to June 2023. Somatic mutations and HR status were detected by BRCA MASTR Plus Dx, Myriad myChoice CDx Plus, Foundation One Medicine or SOPHiA Genetics and germline mutations were detected by Hereditary OncokitDx. Pathologic tumor response was evaluated using CRS (CRS1=no/minimal response; CRS2=appreciable response; CRS3=complete/near-complete response). Primary end point was Progression Free Survival (PFS) according to CRS (CRS1/2 vs 3) in patients receiving PARPi.
Results
43 patients had high grade serous AOC and 2 had high grade endometroid AOC. 32 were stage III and 13 stage IV. 13 had CRS3 and 31 had CRS1/2, 1 undetermined. 36 (80%) had complete resection. Considering the entire population, 24.4% of tumors were BRCAmut and 37% had HRD status. 22 patients (48%) received PARPi (2 olaparib, 10 niraparib). Out of this 22: 12 had CRS3 and 10 had CRS1/2. PFS according to CRS in patients receiving PARPi were: BRCAmut & CRS3 23 months versus 43 months for the BRCAmut & CRS1/2 (p=0.49); HRD & CRS3 24 months versus 43 months for the HRD & CRS1/2 (p=0.47); HR proficient (HRP) & CRS3 25 months versus 13 months for the HRP & CRS1/2 (p=0.19).
Conclusions
Due to small sample, we did not find any statistical differences on PFS in the different subgroups. Contrary to expectations, we did observe a tendency of longer PFS in CRS1/2 versus CRS3 for BRCAmut and HRD tumors, indicating no added value for CRS in these situations. In contrast, a tendency of better PARPi response in the CRS3 versus CRS1/2 was noticed in HRP subgroup, suggesting that platinum sensitivity according to CRS could predict a better PARPi response in HRP population.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E.M. Vida Navas: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Other, travel/accommodation/expense: GSK, AstraZeneca. E.M. Guerra Alia: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca-MSD, PharmaMar, Roche, GSK-Tesaro, Clovis and Eisai; Financial Interests, Personal, Other, travel/accommodation/expense: Roche, GSK-Tesaro, Baxter. M. Gion Cortes: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Gilead, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Travel grants: Roche, Pfizer, Daiichi Sankyo, AstraZeneca. M. Fernandez Abad: Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly, AstraZeneca, Daiichi Sankyo. C. Saavedra Serrano: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Other, Travel grants: Pfizer, AstraZeneca, Novartis, Pfizer. N. Martinez: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Lilly, AstraZeneca, Daiichi Sankyo, GSK-Tesaro, Clovis Oncology, Eisai. E. López-Miranda: Financial Interests, Personal, Advisory Board: AstraZeneca, Seagen. A. Cortes Salgado: Financial Interests, Personal, Advisory Role: GSK, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Speaker’s Bureau: GSK, AstraZeneca, MSD, Eisai, Accord Healthcare, Pfizer; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, travel/accommodation/expense: Pfizer, GSK. All other authors have declared no conflicts of interest.