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

Angelina Tjokrowidjaja, Chee K Lee, Michael Friedlander, Val Gebski, Laurence Gladieff, Jonathan Ledermann, Richard Penson, Amit Oza, Jacob Korach, Tomasz Huzarski, Luis Manso, Carmela Pisano, Rebecca Asher, Sarah J Lord, Se Ik Kim, Jung-Yun Lee, Nicoletta Colombo, Tjoung-Won Park-Simon, Keiichi Fujiwara, Gabe SonkeIgnace Vergote, Jae-Weon Kim, Eric Pujade-Lauraine

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalEur. J. Cancer
Volume139
DOIs
Publication statusPublished - Nov 2020

Keywords

  • 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
  • Organoplatinum Compounds/therapeutic use
  • Ovarian Neoplasms/drug therapy
  • Phthalazines/therapeutic use
  • Piperazines/therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
  • Response Evaluation Criteria in Solid Tumors

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