Utility of CA125 KELIM in predicting benefit from hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer: pooled analysis of KGOG3042 and KOV-HIPEC-01

Objective: Hyperthermic intraperitoneal chemotherapy (HIPEC) administered during interval cytoreductive surgery has shown survival benefits in advanced ovarian cancer. However, predictive biomarkers to guide patient selection for HIPEC are lacking. We evaluated the prognostic and predictive value of the modeled CA125 elimination rate constant K (KELIM), a surrogate marker of tumor chemosensitivity, in relation to the benefit of HIPEC. Methods: This pooled analysis included patients from the KOV-HIPEC-01 phase III trial and the KGOG3042 cohort study. KELIM values were estimated using CA125 kinetics during neoadjuvant chemotherapy. Patients were stratified by KELIM score as favorable (≥1.0) or unfavorable (<1.0). The impact of HIPEC on progression free survival and overall survival was evaluated using univariable and multivariable Cox regression analyses. Results: KELIM was assessable in 213 patients. In those with an unfavorable KELIM score, HIPEC significantly improved progression free survival (20.04 vs 10.25 months; HR 0.42, 95% CI 0.25 to 0.71) and overall survival (not reached vs 45.5 months; HR 0.29, 95% CI 0.12 to 0.73). No significant benefit from HIPEC was observed in patients with a favorable KELIM score. Subgroup analyses revealed that the benefit of HIPEC in patients with an unfavorable KELIM was more pronounced in those with high-grade serous carcinoma, BRCA1/2 wild-type status, age >60 years, and stage IV disease. Conclusions: HIPEC may provide survival benefit primarily in patients with an unfavorable KELIM score. KELIM may be a clinically useful biomarker to guide patient selection for HIPEC during interval cytoreductive surgery in advanced ovarian cancer.