793P - Strong relationships between the CA-125 KELIM score and the tumor biological effects after neo-adjuvant chemotherapy in advanced ovarian cancer patients: CHIVA trial (GINECO)

Background

The modeled CA-125 longitudinal kinetic parameter KELIM^TM during 1st-line chemotherapy is as a pragmatic indicator of the tumor primary chemosensivitiy. However, the links between KELIM^TM and the beneath chemotherapy-induced tumor biological effects had to be explored. We studied the links between KELIM^TM values and pathological response, and changes in TILs, in ovarian cancer patients treated with neo-adjuvant chemotherapy (NACT) +/- interval debulking surgery (IDS).

Methods

In the randomized phase II trial CHIVA (NCT01583322), 188 patients were treated with NACT carboplatin-paclitaxel +/- nintedanib, +/- IDS. Patient KELIMs were previously calculated. The pathological response was assessed with the Chemotherapy Response Score on the omentum (CRS 1-3), and with an enriched pathological response pR score based on the available tumor tissue block when omentum was lacking (pRS 1-3), obtained after NACT. Changes in stromal TILs (sTILs, % of the stromal surface on lymphocytes) and intra-epithelial TILs (ieTILs, qualitative appreciation, 0-2) in baseline tissue and after NACT were analyzed.

Results

A strong association was found between patient KELIM^TM value and the omentum CRS after NACT (n=67; median KELIM^TM, 0.71 for CRS-1; 1.26 for CRS-2; 1.66 for CRS-3; P<0.01). Consistent, a correlation was observed between KELIM and tumor pRS (n=103; median KELIM^TM, 0.73 for pRS-1; 1.25 for pRS-2; 1.61 for pRS-3; P <0.01). At baseline before NACT, no relationships between KELIM^TM and TILs were found. After NACT, a significant association was observed between higher patient KELIM^TM values and higher intra-epithelial TILs infiltrate after NACT (n=99; median KELIM, 0.88 for ieTILs score 0-1; vs 1.26 for ieTILs score 2; P = 0.03).

Conclusions

High consistency was found between patients KELIM^TM and the pathological response after neo-adjuvant chemotherapy, assessed with the omentum CRS score, or the larger tumor pRS score. Omentum may not necessarily needed to assess the pathological response. Intra-epithelial TILs change after NACT was strongly associated with KELIM^TM-assessed chemosensitivity, thereby opening hypotheses about mechanisms of platinum-sensitivity.

Clinical trial identification

NCT01583322.

Editorial acknowledgement

Legal entity responsible for the study

ARCAGY-GINECO (Paris, France).

Funding

Hospital de la Timone (Marseille, France) and Université Claude Bernard Lyon 1 (Lyon, France).

Disclosure

G. Ferron: Financial Interests, Advisory Board: Olympus, AstraZeneca, MSD, Clovis Oncology, Rand-biotech; Financial Interests, Other, Honoraria: Olympus, AstraZeneca, MSD, Roche, Clovis Oncology, EISAI, GSK Tesaro, RanD Biotech; Financial Interests, Other, R&D contract: Olympus; Financial Interests, Other, Educational courses: Olympus, Rand-biotech; Financial Interests, Funding, Congress Funding: AstraZeneca, MSD, Roche, PharmaMar, EISAI, GSK Tesaro. 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; 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. P. Combe: Financial Interests, Advisory Board: AstraZeneca, BMS, MSD, EISAI, SANOFI, Novartis, Daiichi Sankyo, Clovis Oncology, GSK, Amgen; Financial Interests, Other, Investigator in clinical trial: MSD, Novartis, AstraZeneca, BMS. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, Ipsen, BMS, Bayer, Eisai; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Astellas; Financial Interests, Institutional, Coordinating PI: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Other, Travel: MSD, GSK. C. Lebreton: Financial Interests, Personal, Advisory Board: GSK, MSD, Eisai, Clovis Oncology. J. Alexandre: Financial Interests, Personal, Advisory Board: Eisai, MSD, GSK, Janssen, Pfizer; 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. P. Follana: Financial Interests, Personal, Invited Speaker: GSK, Eisai, MSD; Financial Interests, Personal, Advisory Board: Clovis, AZ, Novartis; Financial Interests, Personal, Other, Congress invitation: Gilead. B. You: Financial Interests, Personal, Advisory Board: AZ, MSD, Roche, GSK, Eisai, Seagen, Bayer, Novartis, Amgen, Clovis, BMS, Myriad, Menarini, Gilead. All other authors have declared no conflicts of interest.