Abstract 751P
Background
In patients with advanced high-grade ovarian cancer, the modeled CA-125 ELIMination rate constant K (KELIM) calculated during first-line chemotherapy was associated with overall survival (OS) in 6 independent datasets. We aimed to assess KELIM prognostic and surrogate values in the GCIG mega-database (MAOV), an individual patient data meta-analysis of randomized trials conducted before the PARP-inhibitor era (Paoletti, 2020).
Methods
The CA-125 profiles of patients from MAOV with ≥ 3 CA-125 values during the first 100 days of chemotherapy were analyzed using the nonlinear mixed-effect model to estimate individual KELIM. KELIM was standardized (std) by the median KELIM value and categorized as unfavorable or favorable (< or ≥ 1) for prognostic value assessment. The meta-analytic approach (Buyse, 2000) was used to assess continuous KELIM surrogacy for OS.
Results
Data of 5,690 and 5,842 patients from 8 randomized clinical trials were assessed for OS and PFS analyses. Median follow-up for OS was 50.5 months. Favorable KELIM was significantly associated with longer PFS (median PFS: 30.6 vs 10.3 months, HR 0.50 [0.44-0.57]), longer OS (median OS: 80.0 vs 30.4 months, HR 0.45 [0.37-0.54]), and with higher probability of long complete remission ≥ 5 years (OR 3.63: [2.88-4.38]), together with FIGO stage in multivariate analyses. KELIM exhibited higher prognostic values than the GCIG CA-125 response criterion regarding OS (continuous KELIM C-index: 0.68 [0.67-0.69] vs 0.57 [0.56-0.58], P <0.001). KELIM prognostic value was also confirmed in patients with normal baseline CA-125 values (< 35 IU/mL). However, KELIM surrogacy for OS was not established, due to the narrow range of treatment effects and the negativity of experimental arms in collected trials (individual τ= 0.29 [0.27-0.31], R2 trial = 0.04 [0-0.32]).
Conclusions
In this mega-database, KELIM surrogacy was not found, probably as a result of the lack of positive trials. However, the independent prognostic value of KELIM on OS and PFS was identified, including in patients with baseline normal-range CA-125 values, and appeared more discriminant than the GCIG CA-125 response criterion.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gynecological Cancer InterGroup.
Funding
Gynecological Cancer InterGroup, Hospices Civils de Lyon.
Disclosure
B. you: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK-Tesaro; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Roche-Genentech; Financial Interests, Personal, Advisory Board: ECS Progastrine; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: LEK; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Merck Serono. R.M. Glasspool: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Advisory Board: GSK/Tesaro; Financial Interests, Personal, Invited Speaker: GSK/Tesaro; Financial Interests, Personal, Funding: GSK/Tesaro; Financial Interests, Personal, Advisory Role: Sotio; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Institutional, Research Grant: Clovis Oncology; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Lilly/Ignyta; Financial Interests, Institutional, Principal Investigator: Lilly/Ignyta; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Clovis Oncology; Financial Interests, Institutional, Principal Investigator: Immunogen; Non-Financial Interests, Personal, Member of the Board of Directors: NCRI Ovarian Group; Non-Financial Interests, Personal, Leadership Role: SGCTG Ovarian; Non-Financial Interests, Personal, Leadership Role: IGCS; Non-Financial Interests, Personal, Expert Testimony, Gyn cancer faculty: ESMO; Non-Financial Interests, Personal, Member of the Board of Directors: GCIG Meta-Analysis Group; Non-Financial Interests, Personal, Member of the Board of Directors: ENGOT ealy phase; Non-Financial Interests, Personal, Advisory Board: target Ovarian Cancer; Non-Financial Interests, Personal, Expert Testimony, Expert Panel Member: Horizons. A.V. Tinker: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Research Grant: AstraZeneca; Non-Financial Interests, Personal and Institutional, Speaker’s Bureau: GSK; Non-Financial Interests, Personal and Institutional, Advisory Role: GSK; Non-Financial Interests, Personal and Institutional, Leadership Role: CCTG. K. Lindemann: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Research Grant: GSK; Financial Interests, Institutional, Other: GSK; Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Institutional, Other: Vaccibody; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Takeda; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Other: MSD; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: Takeda; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: GSK; Non-Financial Interests, Personal, Principal Investigator: Vaccibody; Non-Financial Interests, Personal, Member of the Board of Directors: NSGO. I.L. Ray-Coquard: Financial Interests, Personal, Other, Travel: AstraZeneca; Financial Interests, Personal, Other, Travel: GSK; Financial Interests, Personal, Other, Travel: Clovis; Financial Interests, Personal, Other, Travel: Roche; Financial Interests, Personal, Other: Mersana; Financial Interests, Personal, Other: Deciphera; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: Onxena; Financial Interests, Personal, Other: Aravive. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Biocad; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: Karyopharm; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Riche; Financial Interests, Personal, Advisory Board: Zailab; Financial Interests, Personal, Member of the Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Non-Financial Interests, Institutional, Research Grant: Apexigen; Non-Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Institutional, Project Lead: Deciphera; Non-Financial Interests, Institutional, Research Grant: GSK; Non-Financial Interests, Institutional, Research Grant: Ultimovacs. J. Peron: Financial Interests, Personal, Advisory Role: Fab'entech; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Member: Eisai; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Project Lead: Roche; Non-Financial Interests, Personal, Member: French health national authority. I. McNeish: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: ScanCell; Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Personal, Other: Worldwide Cancer Research. T. Kagimura: Non-Financial Interests, Personal, Member of the Board of Directors: Japanese Society for Pharmacoepidemiology (JSPE). All other authors have declared no conflicts of interest.