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

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.

• Authors: Wassim Abida, Akash Patnaik, David Campbell, Jeremy Shapiro, Alan H Bryce, Ray McDermott, Brieuc Sautois, Nicholas J Vogelzang, Richard M Bambury, Eric Voog, Jingsong Zhang, Josep M Piulats, Charles J Ryan, Axel S Merseburger, Gedske Daugaard, Axel Heidenreich, Karim Fizazi, Celestia S Higano, Laurence E Krieger, Cora N Sternberg, Simon P Watkins, Darrin Despain, Andrew D Simmons, Andrea Loehr, Melanie Dowson, Tony Golsorkhi, Simon Chowdhury, TRITON2 investigators
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 32 Pg. 3763-3772 (11 10 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 32795228 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

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