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CA-125 KELIM as a Potential Complementary Tool for Predicting Veliparib Benefit: An Exploratory Analysis From the

Benoit You1,2, Vasudha Sehgal3, Balakrishna Hosmane3

  • 1Faculté de Médecine Lyon-Sud, EA 3738 CICLY, Univ Lyon, Université Claude Bernard Lyon 1, GINECO, Lyon, France.

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The cancer antigen (CA)-125 elimination rate constant K (KELIM) predicts benefit from veliparib in ovarian cancer. Favorable KELIM indicates higher chemosensitivity and improved progression-free survival (PFS) with veliparib, especially in HRD or BRCA-mutated tumors.

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Area of Science:

  • Oncology
  • Pharmacology
  • Biomarkers

Background:

  • High-grade ovarian carcinomas pose significant treatment challenges.
  • Veliparib, a poly (adenosine diphosphate-ribose) polymerase inhibitor, is investigated in combination therapies.
  • Cancer antigen (CA)-125 kinetics can reflect tumor chemosensitivity.

Purpose of the Study:

  • To evaluate the prognostic value of the CA-125 elimination rate constant K (KELIM) in predicting veliparib treatment benefit.
  • To explore the association between KELIM and progression-free survival (PFS) in ovarian cancer patients treated with veliparib.
  • To determine if KELIM can complement homologous recombination (HR) status in predicting response to veliparib.

Main Methods:

  • Analysis of CA-125 longitudinal data from 854 ovarian cancer patients in the VELIA trial.
  • Estimation of individual KELIM values to categorize patients into favorable (≥ median) or unfavorable (< median) groups.
  • Exploration of KELIM's prognostic value across different surgical approaches, risk groups, and HR statuses (BRCA mutation, HR deficiency [HRD], or HR proficiency [HRP]).

Main Results:

  • Increasing KELIM values correlated with greater veliparib benefit in HRD ovarian cancer.
  • Decreasing KELIM values were associated with benefit in HR-proficient (HRP) cancer.
  • The highest PFS benefit was observed in patients with favorable KELIM and BRCA mutation or BRCA wild-type HRD cancer.
  • Patients with BRCA mutation and unfavorable KELIM had a high progression rate (74%) within 18 months.

Conclusions:

  • KELIM serves as a prognostic marker for veliparib efficacy in ovarian cancer, complementing HR status.
  • Tumor chemosensitivity, as indicated by KELIM, is a crucial factor in determining response to poly (adenosine diphosphate-ribose) polymerase inhibitors.
  • KELIM may help identify patients most likely to benefit from veliparib, particularly in conjunction with HR status.