Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration

J Clin Oncol. 2020 Nov 10;38(32):3763-3772. doi: 10.1200/JCO.20.01035. Epub 2020 Aug 14.

Abstract

Purpose: BRCA1 or BRCA2 (BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study.

Methods: We enrolled patients who progressed after one to two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate.

Results: Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients).

Conclusion: Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Clinical Trials, Phase II as Topic
  • Germ-Line Mutation
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Progression-Free Survival
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Indoles
  • Poly(ADP-ribose) Polymerase Inhibitors
  • rucaparib