The following is a summary of “CA-125 KELIM as a Potential Complementary Tool for Predicting Veliparib Benefit: An Exploratory Analysis From the VELIA/GOG-3005 Study,” published in the January 2023 issue of Oncology by You, et al.
In the VELIA study, veliparib in combination with carboplatin-paclitaxel, followed by maintenance (veliparib-throughout), was linked to a better progression-free survival (PFS) in patients with high-grade ovarian carcinomas than carboplatin-paclitaxel alone. For a study, researchers sought to determine the prognostic significance of the cancer antigen (CA)-125 elimination rate constant K (KELIM), which was known to be a marker of the intrinsic tumor chemosensitivity (the higher the KELIM, the higher the chemosensitivity; the faster the rate of CA-125 drop).
The KELIM values of each individual were calculated using the longitudinal CA-125 kinetics. Patients were divided into groups according to whether their KELIM was favorable (≥median) or unfavorable (<median). In cohorts treated with major or interval debulking surgery, the predictive significance of KELIM for veliparib-related PFS benefit was investigated, depending on the degree of surgical completion, the disease progression risk group, and the homologous recombination (HR) status (BRCA mutation, HR deficiency [HRD], or HR proficiency [HRP]).
Of the 1,140 patients who were recruited, data from 854 individuals (854 primary debulking surgeries and 154 interval debulking surgeries) were evaluated. In HRD cancer, higher KELIM levels were linked to greater veliparib benefit, but lower KELIM values were linked to greater veliparib benefit in HRP cancer. The greatest PFS benefit from veliparib was seen in patients who had both a favorable KELIM and BRCA mutation (hazard ratio, 0.28; 95% CI, 0.13 to 0.61) or BRCA wild-type HRD cancer (hazard ratio, 0.43; 95% CI, 0.26 to 0.70), which is consistent with the link between the effectiveness of poly (adenosine diphosphate-ribose) polymerase inhibitors and platinum sensitivity. On the other hand, when using veliparib, 74% of patients with a BRCA mutation and an unfavorable KELIM progressed within 18 months. The veliparib chemosensitizing action could have helped the patients with HRP cancer with unfavorable KELIM.
The primary tumor chemosensitivity found after the first-line chemotherapy may be another supplementary factor determining the effectiveness of poly (adenosine diphosphate-ribose) polymerase inhibitors in addition to HRD/BRCA status.