Abstract 793P
Background
The modeled CA-125 longitudinal kinetic parameter KELIMTM during 1st-line chemotherapy is as a pragmatic indicator of the tumor primary chemosensivitiy. However, the links between KELIMTM and the beneath chemotherapy-induced tumor biological effects had to be explored. We studied the links between KELIMTM 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 KELIMTM value and the omentum CRS after NACT (n=67; median KELIMTM, 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 KELIMTM, 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 KELIMTM and TILs were found. After NACT, a significant association was observed between higher patient KELIMTM 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 KELIMTM 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 KELIMTM-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.
Resources from the same session
628P - Immunotherapy in mismatch repair-deficient metastatic colorectal cancer: Long-term outcome and novel predictive markers
Presenter: Amos Stemmer
Session: Poster session 11
629P - First results of the french prospective cohort of colorectal cancers with microsatellite instability (COLOMIN2)
Presenter: David Tougeron
Session: Poster session 11
630P - Determining a prognostic score using imaging to assess the benefit of combo anti-PD1 + anti-CTL4 vs anti-PD1 in patients with metastatic MSI/dMMR colorectal cancer (mCRC MSI)
Presenter: Remy Barbe
Session: Poster session 11
631P - Using the unique somatic mutation profile of POLE loss of proof-reading mutation helps in selection of patients who may benefit from immunotherapy
Presenter: Giulia Maddalena
Session: Poster session 11
632P - Predictive value of C-reactive protein (CRP) in microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) patients given first-line alternating short-course oxaliplatin-based chemotherapy (FLOX) and nivolumab
Presenter: Sebastian Meltzer
Session: Poster session 11
633P - Genomic alterations in SPEN predict outcome of immune checkpoint therapy in gastrointestinal cancer
Presenter: Changxiong Wu
Session: Poster session 11
634P - The ave-rec phase II trial of PD-L1/PD-1 blockade with avelumab plus chemoradiotherapy for resectable ESMO high risk rectal cancers
Presenter: Michael Michael
Session: Poster session 11
635P - Avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for the treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): The AVETUXIRI phase II study
Presenter: Marc van den Eynde
Session: Poster session 11