773P - Role of tumor primary chemosensitivity assessed by modeled CA-125 KELIM to predict complete interval debulking surgery (IDS) in ovarian carcinoma patients treated with neo-adjuvant chemotherapy and immunotherapy: A GINEGEPS/GINECO study of the NeoPembrOv and INeOV trials

Background

In patients with advanced epithelial ovarian carcinoma treated with neo-adjuvant chemotherapy (NACT), increasing chemotherapy efficacy is critical to improve the likelihood of complete IDS. The utility of adding immune checkpoint inhibitors (ICI) to NACT was assessed in the randomized NeoPembrOv (NCT 03275506) and INeOV (NCT 03249142) trials. We aimed to determine whether tumor chemosensitivity assessed by the modeled CA-125 KELIM (Lauby et al, 2021), calculated during neoadjuvant treatment, would identify the patients who benefited most from ICI regarding IDS success.

Methods

We retrospectively estimated the modeled longitudinal CA-125 KELIM values in patients enrolled in NeoPembrOV and INeOV trials. The ability of KELIM to predict IDS success after NACT +/- ICI was assessed using a univariate and multivariate Cox proportional-hazards model, adjusted for FIGO stage, histological subtype, BCRA mutational status, and PDL1 expression (CPS). The IDS success was characterized by 1) surgery completeness (CC0 resection vs surgical residual/no IDS); 2) pathologic response in ovaries and in peritoneum (complete vs partial).

Results

KELIM was estimated in 88 (97%) and 67 (96%) patients enrolled in NeoPembrOV and INeOV trials, respectively. The median KELIM values were not impacted by the addition of ICI (in NeoPembrOv trial: 0.052 d^-1 and 0.055 d^-1 in the control and experimental groups, respectively, p=0.424; in INeOV trial: 0.047 d^-1). The independent prognostic value of KELIM regarding the IDS success was confirmed regardless of ICI addition: 1) Likelihood of achieving a CC0 resection (OR 22.7, 95% CI [6.9 – 111.1], P < 0.0001); 2) Probability of achieving a complete pathological response (OR 14.2, 95% CI [3.7 – 68.5], P = 0.0003). However, KELIM did not discriminate patients who benefited more from ICI addition for IDS success.

Conclusions

Whilst the modeled CA-125 KELIM calculated during the neoadjuvant treatment can predict the success of IDS, it did not identify a subpopulation of patients who derived a higher benefit from the addition of ICI to NACT for IDS success.

Clinical trial identification

NCT03275506 and NCT03249142.

Editorial acknowledgement

Legal entity responsible for the study

ARCAGY GINECO.

Funding

MSD, AstraZeneca.

Disclosure

P. Corbaux: Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Institutional, Local PI: Sensorion, Roche, Novartis, MSD. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape; Financial Interests, Personal, Writing Engagement, Educational: Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: OWKIN; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AZ; Financial Interests, Institutional, Funding, CI clinical trial: AZ; 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; Non-Financial Interests, Member: GCIG. O. Le Saux: Financial Interests, Personal, Advisory Board: Novartis, MSD, GSK; Financial Interests, Personal, Invited Speaker: Lilly, AstraZeneca, Clovis; Financial Interests, Institutional, Trial Chair: Novartis, Hospira-Pfizer foundation, Astellas. L. Collet: Other, congress and travel: AstraZeneca, GSK, PharmaMar. L. Bengrine Lefevre: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, MSD. C. Blonz: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Lilly, MSD, Pfizer, AstraZeneca. F. Priou: Financial Interests, Personal, Advisory Board: Daiichi; Non-Financial Interests, Personal, Other, congress travel: Novartis. J. Alexandre: Financial Interests, Personal, Advisory Board: Eisai, MSD, GSK, Janssen, Pfizer, Seagen; Financial Interests, Personal, Invited Speaker: Eisai, MSD, AstraZeneca, GSK, Novartis; Financial Interests, Institutional, Research Grant: Janssen, GSK, MSD; Financial Interests, Institutional, Local PI: MSD, Eisai, Agenus, GSK, ImmunoGen, Incyte; Financial Interests, Institutional, Coordinating PI: Kartos. N. Cloarec: Non-Financial Interests, Principal Investigator, clinical studies: MSD; Non-Financial Interests, Principal Investigator: AZD, Novartis, Roche, Takeda, BMS; Other, Medical Meeting: Takeda. C. Lebreton: Financial Interests, Personal, Advisory Board: GSK, GSK, MSD, Eisai, Clovis Oncology. B. You: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, Bayer, Roche, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad, Menarini, Gilead, Eisai, Pharma&.. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmun, Eisai, Sutro, BMS, Adaptimmune, Daichi Sankyo, ImmunoGen, Seagen, PMV Pharma; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. All other authors have declared no conflicts of interest.