Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer

Sci Rep. 2024 Jul 29;14(1):17459. doi: 10.1038/s41598-024-68338-2.

Abstract

We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively. Univariate and multivariate analyses showed that GCIG CA125 response (n = 32) is associated with improved progression-free survival (PFS) and overall survival (OS) compared to no GCIG CA125 response (n = 40) (median PFS 8.0 vs. 3.5 months [HR: 0.30, 95% CI: 0.18-0.51, p < 0.0001]; median OS 19.8 vs. 10.0 months [HR: 0.38, 95% CI: 0.23-0.64, p < 0.001]) independent of BRCA mutation status, platinum-sensitivity, previous PARP inhibitor therapy, ECOG performance status, and FIGO stage. Notably, GCIG CA125 response had a high negative predictive value (NPV: 93%, 95% CI: 80-98), but poor positive predictive value (PPV: 53%, 95% CI: 35-71) in predicting RECIST response. CA125 PD criteria also showed poor concordance with RECIST PD (PPV 56%, 95% CI: 40-71; NPV 33%, 95% CI: 17-54). Therefore, serum CA125 may be useful as a highly accessible prognostic and predictive biomarker to CHK1i therapy in recurrent HGSOC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • CA-125 Antigen* / blood
  • Checkpoint Kinase 1* / antagonists & inhibitors
  • Female
  • Humans
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Ovarian Neoplasms* / blood
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Prognosis
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Response Evaluation Criteria in Solid Tumors

Substances

  • CA-125 Antigen
  • Checkpoint Kinase 1
  • CHEK1 protein, human
  • prexasertib
  • Pyrazoles
  • Pyrazines
  • Protein Kinase Inhibitors
  • MUC16 protein, human
  • Biomarkers, Tumor
  • Membrane Proteins