The modeled CA-125 elimination rate constant k (KELIM) score as a predictor of treatment response in patients with advanced high grade serous ovarian cancer (190)

Abstract

Objectives: A subset of patients with high-grade serous ovarian cancer (HGSOC) treated with neoadjuvant chemotherapy (NACT) has a disease that is resistant or refractory to treatment. The objective of this study was to externally validate the KELIM score in this patient cohort compared to patients with the platinum-sensitive disease and to determine whether the KELIM score is predictive of platinum sensitivity, progression-free (PFS), and overall survival (OS). Methods: This is a retrospective cohort study of NACT patients with Stage III-IV HGSOC diagnosed between January 1, 2010, and December 31, 2019, at a tertiary cancer center. KELIM score was calculated using at least three CA-125 values within the first 100 days of chemotherapy using a validated calculation formula [https://www.biomarker-kinetics.org/CA-125-neo], notably pre-cycle 2, 3 and 4. Demographic parameters were collected, and Kaplan-Meier survival analyses were performed for PFS and OS. This study was approved by the local ethics board. Results: A total of 217 patients met inclusion criteria and were included in the final analysis. Median follow-up was 28.93 months (range: 2.86-135.06). There was no significant difference in stage, functional status, cytoreductive outcome, or BRCA mutation status (germline or somatic) between patients with a KELIM ≥1 and <1. Patients with a KELIM ≤1 had a lower median baseline CA-125 (1077 vs 1765, p=0.024), no significant difference in CA-125 at cycle 2 (438 vs 967, p=0.79) and significantly higher CA-125 level at cycle 3 (228 vs 68, p<0.001) and cycle 4 (105.5 vs 26, p<0.001) compared to patients with KELIM ≥1. KELIM score <1 was associated with lower median PFS (13.58 vs 19.69, p<0.001) as compared to KELIM ≥1 and a lower median platinum-free interval (PFI) (7.66 vs 13.64, p<0.001). The 5-year OS was significantly lower in patients with a KELIM score <1 as compared to patients with a KELIM score ≥1 (57% vs 72%, p=0.014). After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase (parp)-inhibitor use, and BRCA status, patients with KELIM score <1 had an HR of 1.57 (95% CI: 1.08-2.28) for disease progression and HR of 1.99 (95% CI: 1.01-3.95) for death compared to patients with KELIM score ≥1. BRCA status was independently associated with an increase in KELIM score (odds ratio (OR): 1.917, 95% CI: 1.046-3.512, p=0.035).[Formula presented] Conclusions: Patients with advanced HGSOC undergoing NACT with a calculated KELIM score <1 were more likely to have a platinum-resistant disease, worse PFS, and worse OS when compared to patients with a KELIM score ≥1. The KELIM score can be a helpful tool to predict chemotherapy sensitivity and survival outcomes in this patient population and may aid in treatment decision-making.