Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy

Eur J Cancer. 2020 Nov;139:59-67. doi: 10.1016/j.ejca.2020.08.021. Epub 2020 Sep 23.


Background: Limited evidence exists to support CA-125 as a valid surrogate biomarker for progression in patients with ovarian cancer on maintenance PARP inhibitor (PARPi) therapy. We aimed to assess the concordance between CA-125 and Response Evaluation Criteria in Solid Tumours (RECIST) criteria for progression in patients with BRCA mutations on maintenance PARPi or placebo.

Methods: We extracted data on progression as defined by Gynecologic Cancer InterGroup CA-125, investigator- and independent central-assessed RECIST from the SOLO2/ENGOT-ov21(NCT01874353) trial. We excluded those with progression other than by RECIST, progression on date of randomisation, and no repeat CA-125 beyond baseline. We evaluated the concordance between CA-125 progression and RECIST progression, and assessed the negative (NPV) and positive predictive value (PPV).

Results: Of 295 randomised patients, 275 (184 olaparib, 91 placebo) were included. 171 patients had investigator-assessed RECIST progression. Of 80 patients with CA-125 progression, 77 had concordant RECIST progression (PPV 96%, 95% confidence interval 90-99%). Of 195 patients without CA-125 progression, 94 had RECIST progression (NPV 52%, 45-59%). Within treatment arms, PPV was similar (olaparib: 95% [84-99%], placebo: 97% [87-100%]) but NPV was lower in patients on placebo (olaparib: 60% [52-68%], placebo: 30% [20-44%]). Of 94 patients with RECIST but without CA-125 progression, 64 (68%) had CA-125 that remained within normal range. We observed similar findings using independent-assessed RECIST.

Conclusions: Almost half the patients without CA-125 progression had RECIST progression, and most of these had CA-125 within the normal range. Regular computed tomography imaging should be considered as part of surveillance in patients treated with or without maintenance olaparib rather than relying on CA-125 alone.

Keywords: BRCA mutation; CA-125; CT; Olaparib; Ovarian cancer; Poly(ADP-Ribose) polymerase inhibitors; Response evaluation criteria in solid tumours.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • CA-125 Antigen / metabolism*
  • Disease Progression
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Female
  • Germ-Line Mutation / genetics
  • Humans
  • Maintenance Chemotherapy / methods
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology*
  • Organoplatinum Compounds / therapeutic use
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Phthalazines / therapeutic use*
  • Piperazines / therapeutic use*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Response Evaluation Criteria in Solid Tumors


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Fanconi Anemia Complementation Group Proteins
  • Organoplatinum Compounds
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • olaparib

Associated data