Data from CA-125 ELIMination Rate Constant K (KELIM) Is a Marker of Chemosensitivity in Patients with Ovarian Cancer: Results from the Phase II CHIVA Trial

Abstract

<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin–paclitaxel regimen ± nintedanib, and IDS, <i>n</i> = 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.</p>Results:<p>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 = 0.13; 95% confidence interval (CI), 0.03–0.49] and complete IDS (no vs. yes, OR = 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.</p>Conclusions:<p>The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (<a href="http://www.biomarker-kinetics.org/CA-125-neo" target="_blank">http://www.biomarker-kinetics.org/CA-125-neo</a>), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance.</p><p><i>See related commentary by May and Oza, p. 4432</i></p></div>

Circulating serum miRNAs predict response to platinum chemotherapy in high-grade serous ovarian cancer

“…Indicators that might define platinum treatment response in ovarian cancer include TFIp, response rate, and progression-free survival [24,36,37]. Biomarkers that can predict platinum response should be able to predict TFIp in first-line therapy because TFIp is expected.…”