5134 - Early prediction of the platinum-resistant relapse risk using the CA125 modeled kinetic parameter KELIM: a pooled analysis of AGO-OVAR 7 & 9; ICON 7 (AGO/GINECO/ MRC CTU/GCIG trials).

Background

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 1^st 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.

Methods

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.

Results

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).

Conclusions

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 1^st line setting.

Clinical trial identification

Editorial acknowledgement

No assistance

Legal entity responsible for the study

ARCAGY-GINECO.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.