Platinum-resistant relapse after 1st line treatment (platinum-free interval < 6 months) is a very detrimental event for patient survival. The modeled CA125 elimination parameter KELIM calculated during the first 100 chemotherapy days is a predictive factor of PFS/OS in 1st line treatment (Colomban et al. Clin Cancer Res 2019). KELIM was associated with the risk of subsequent platinum-resistant relapse (PtRR) in neoadjuvant setting (Robelin et al. Proc ASCO 2019). The objective was to validate the predictive value of KELIM in 1st line treatment (with primary debulking surgery) on the data of 3 large phase III trials, and to integrate it in a Platinum-Resistant Recurrence Score.
Data from AGO-OVAR 9 (carboplatin-paclitaxel (CP) +/- gemcitabine); AGO-OVAR 7 (CP +/- topotecan); and ICON 7 trials (CP +/- bevacizumab) were analyzed. The predictive value of individual modeled KELIM regarding the risk of subsequent PtRR was assessed with other prognostic factors (stages; histological subtypes; grades; arms; GCIG CA125 criteria; Oza groups in ICON 7) using multivariate ROC curve & logistic models.
Among assessable 2868 patients, 208 patients experienced subsequent PtRR (7.2%). Median KELIM (days-1) gradually increased with the subsequent PFIs: <6 months, 0.043; 6-12 months, 0.052; > 12 months, 0.065 (P < 0.05). Using multivariate logistic models, 3 covariates were significantly associated with PtRR risk: continuous KELIM (OR, 0.17 95% CI [0.11-0.25]; disease stage III (OR, 7.51 [3.70-18.02]); or stage IV (OR, 19.28 [9.06-47.80]); or Oza high risk group in ICON7 (OR 2.35 [1.79-3.10]). They were integrated in a Platinum-Resistant Recurrence Score meant to predict the individual risk of subsequent PtRR (i.e. risk calculated at 60% if KELIM = 0.2 and stage III).
Modeled KELIM, easily calculable online with three CA125 values observed during the first 100 adjuvant chemotherapy days (http://www.biomarker-kinetics.org/), is related to primary chemoresistance and survival. It has been integrated in a Platinum Resistant Recurrence Score that predicts the individual risk of PtRR in 1st line setting.
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All authors have declared no conflicts of interest.