46MO - What are the predictors of the success of interval debulking surgery (CC0-IDS) in patients with advanced ovarian cancers? Consistent data from two large independent datasets

Background

Over 50% of advanced epithelial ovarian cancer patients undergo neoadjuvant chemotherapy (NACT), aiming to achieve a complete interval debulking surgery (IDS). Understanding the factors that can predict IDS success is crucial.

Methods

The French GINECO and the Gemelli (Italy) groups analyzed two independent datasets, separately. The French dataset included 133 patients from the CHIVA (C) randomized phase II trial (NCT01583322). The Italian dataset was built with the Policlinico GEMELLI (G) real-life registry with 357 patients (ID5936–ProtN45). Univariate/multivariate logistic regression models were performed to examine the clinical and biological covariates associated with: 1) low peritoneal carcinomatosis index (PCI) after 3/4 NACT cycles (Sugarbaker PCI ≤ 10 or Fagotti score at IDS ≤ 2); 2) IDS with no macroscopic residual lesion (CC0), 3) Complete or near-complete pathological response according to chemotherapy response score (CRS3). The assessed predictor factors were the modeled CA-125 longitudinal kinetics parameter KELIM, considered as a continuous (KCont) value or as Favorable (≥ 1; FavK) vs Unfavorable (<1; UnFavK); best radiological response according to RECIST 1.1; and BRCA mutation/homologous recombination deficiency (HRD) status (C: Shallow HRD; G: Myriad&AmoyDx).

Results

Higher KELIM, was the only factor in both the datasets that consistently predicted: - lower PCI after NACT: Odd Ratios (O.R.) KCont: (C) 4.08 [1.78-10.10] - (G) 4.44 [2.09-9.40]; O.R. FavK vs UnFavK: (C) 4.19 [1.76-10.71] - (G) 2.92 [1.58-.39] - higher rates of complete IDS-CC0: O.R. KCont: (C) 7.29 [3.38-17.13] - (G) 4.66 [1.89-11.48]; O.R. FavK vs UnFavK: (C) 4.24 [2.07-8.99] - (G) 3.66 [1.67-8.01] - higher probability of CRS3: O.R. KCont: (C) 12.43 [3.75-55.5] - (G) 2.97 [1.82-4.84]; O.R. FavK vs UnFavK: (C) 21.44 [4.15-394.01] - (G) 2.36 [1.51-3.70]. The best radiological response was inconsistently significant. The BRCA/HRD status was not predictive of IDS success.

Conclusions

Across 2 independent international datasets, the primary tumor’s chemosensitivity, assessed by CA-125 KELIM, was the sole consistent predictor of IDS success after NACT.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Marchetti: Financial Interests, Personal, Advisory Role: Clovis, PharmaMar, GSK, AstraZeneca, MSD; Financial Interests, Personal, Other, Travel and Accommodation: PharmaMar, Roche. A. Fagotti: Financial Interests, Personal, Advisory Board, Advisory Board AstraZeneca: AstraZeneca & MSD; Financial Interests, Personal, Invited Speaker, Speaker: PharmaMar, Johnson & Johnson, Fondazione Internazionale Menarini; Financial Interests, Personal, Invited Speaker, Moderator: GSK; Financial Interests, Institutional, Invited Speaker, NUVOLA trial-NCT04261465: AstraZeneca; Financial Interests, Institutional, Invited Speaker, ENSEAL® X1 Curved Jaw Tissue Sealer: Johnson & Johnson; Financial Interests, Institutional, Invited Speaker, PROTOCOL ID: Microvesicles INnovative OvaRian CAncer (MINORCA). ID2368Studio osservazionale valutante gli esosomi e le microvescicole circolanti con tecnologie innovative in qualità di potenziali biomarcatori per personalizzare il trattamento del carcinoma sieroso di alto grado ovarico: Roche. F. Blanc-Durand: Financial Interests, Institutional, Advisory Role: AstraZeneca/Merck, GSK; Financial Interests, Personal, Advisory Role: Eisai/MSD; Financial Interests, Personal, Other, Travel and Accommodation: GSK; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune. C.M. Sassu: Financial Interests, Personal, Advisory Role: GSK, AstraZeneca. E. Pujade-Lauraine: Financial Interests, Personal, Other, Employement: Arcagy-Gineco; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Merck, Incyte, AGENUS; Financial Interests, Personal, Other, Honoraria: AstraZeneca, GSK; Financial Interests, Institutional, Research Grant: AstraZeneca. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Personal, Member, Board of Directors: GCIG; Other, Personal, Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro, BMS, Adaptimmune, Daiichi Sankyo, Immunogen, Seagen, PMVpharma; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. U. Malapelle: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, GSK, Merck, AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck, AstraZeneca, Janssen, Diatech, Novartis, Hedera, Diatech; Non-Financial Interests, Personal, Leadership Role, Scientific Secretary and Editor in Chief of The Journal of Liquid Biopsy (Official Journal of the Society): ISLB. 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, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: OWKIN; 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: AstraZeneca; 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, Personal, Member: GCIG. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Baxter Healthcare, GSK, Intuitive Surgical Inc., AstraZeneca & MSD, Olympus Europa, GSK, AstraZeneca & MSD, Olympus Europa; Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Invited Speaker, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Invited Speaker, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. B. You: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Novartis, Lek, Tesaro, Bayer, Amgen, Clovis Oncology, GSK, ECS PROGASTRIN, Immunomedics, Daiichi Sankyo Europe GmbH, Myriad Genetics, MSD Oncology, Seagen, Eisai; Financial Interests, Personal, Other, Travel and Accommodation: Roche/Genentech, AstraZeneca, Bristol Myers Squibb, MSD Oncology, Bayer, Seagen; Financial Interests, Institutional, Research Grant: Merck Serono, Roche/Genentech, Clovis Oncology, Novartis. All other authors have declared no conflicts of interest.