TY - JOUR
T1 - CA-125 ELImination rate constant K (KELIM) is a marker of chemosensitivity in patients with ovarian cancer
T2 - Results from the phase II CHIVA trial
AU - You, Benoit
AU - Robelin, Patrick
AU - Tod, Michel
AU - Louvet, Christophe
AU - Lotz, Jean Pierre
AU - Abadie-Lacourtoisie, Sophie
AU - Fabbro, Michel
AU - Desauw, Christophe
AU - Bonichon-Lamichhane, Nathalie
AU - Kurtz, Jean Emmanuel
AU - Follana, Philippe
AU - Leheurteur, Marianne
AU - Piano, Francesco Del
AU - Ferron, Gwenael
AU - de Rauglaudre, Gaëtan
AU - Ray-Coquard, Isabelle
AU - Combe, Pierre
AU - Chevalier-Place, Annick
AU - Joly, Florence
AU - Leary, Alexandra
AU - Pujade-Lauraine, Eric
AU - Freyer, Gilles
AU - Colomban, Olivier
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Purpose: In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical-surgical treatment. Experimental Design: The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin-paclitaxel regimen + nintedanib, and IDS, n ¼ 188 patients). The KELIM predictive value regarding the tumor response rate, likelihood of complete IDS, risk of subsequent platinum-resistant relapse (PtRR), progression-free survival (PFS), and overall survival (OS) was assessed using univariate and multivariate tests. Results: The data from 134 patients were analyzed. KELIM was an independent and major predictor of subsequent PtRR risk, and of survivals. The final logistic regression model, including KELIM [OR ¼ 0.13; 95% confidence interval (CI), 0.03-0.49] and complete IDS (no vs. yes, OR ¼ 0.30; 95% CI, 0.11-0.76) highlights the preponderant role of chemosensitivity on the success of the first-line treatment. In patients with highly chemosensitive diseases, the patient prognosis was driven more by the chemotherapy-induced antitumor effects than by the surgery. Conclusions: The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (http://www.biomarker-kinetics.org/CA-125-neo), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance.
AB - Purpose: In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical-surgical treatment. Experimental Design: The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin-paclitaxel regimen + nintedanib, and IDS, n ¼ 188 patients). The KELIM predictive value regarding the tumor response rate, likelihood of complete IDS, risk of subsequent platinum-resistant relapse (PtRR), progression-free survival (PFS), and overall survival (OS) was assessed using univariate and multivariate tests. Results: The data from 134 patients were analyzed. KELIM was an independent and major predictor of subsequent PtRR risk, and of survivals. The final logistic regression model, including KELIM [OR ¼ 0.13; 95% confidence interval (CI), 0.03-0.49] and complete IDS (no vs. yes, OR ¼ 0.30; 95% CI, 0.11-0.76) highlights the preponderant role of chemosensitivity on the success of the first-line treatment. In patients with highly chemosensitive diseases, the patient prognosis was driven more by the chemotherapy-induced antitumor effects than by the surgery. Conclusions: The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (http://www.biomarker-kinetics.org/CA-125-neo), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance.
UR - http://www.scopus.com/inward/record.url?scp=85088365266&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-0054
DO - 10.1158/1078-0432.CCR-20-0054
M3 - Article
C2 - 32209570
AN - SCOPUS:85088365266
SN - 1078-0432
VL - 26
SP - 4625
EP - 4632
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -