Treatment options for mCRPC following androgen deprivation and taxane therapy are limited. Preclinical and limited clinical data suggest efficacy of PARP inhibition in HRR-deficient PCa.
TRITON2 (NCT02952534; target enrolment, 157 pts) is evaluating rucaparib 600 mg BID in pts with a deleterious germline or somatic alteration in BRCA1, BRCA2 or 1 of 13 other prespecified HRR genes. Pts who progressed on 1–2 lines of androgen receptor–directed therapy and 1 prior line of taxane-based chemotherapy for mCRPC are eligible. The primary endpoint is centrally assessed confirmed objective response rate per modified RECIST v1.1/PCWG3 for pts with measurable disease and confirmed prostate-specific antigen (PSA) response (≥50% decrease) in pts without measurable disease. PSA response in all pts is a secondary endpoint.
At the 6 Mar 2018 data cutoff date, 52 pts were treated with rucaparib. Median duration of follow-up was 3.7 mo (range, 1.0–12.6). Twenty-six pts (50%) had a BRCA1/2 alteration (BRCA pts), 12 had a CDK12 alteration, 10 had an ATM alteration and 4 had an alteration in another HRR gene. Prior therapies included docetaxel (88.5%), enzalutamide (82.7%), abiraterone (71.2%) and cabazitaxel (11.5%). Forty-four pts (84.6%) had bone metastases; 33 (63.5%) and 17 pts (32.7%) had nodal and visceral metastases, respectively. Among BRCA pts, 21 (80.8%) remain on study (median treatment duration, 16.1 wk; range, 4.1–36.9). Eleven of 23 evaluable BRCA pts had a confirmed PSA response (47.8%; 95% CI, 26.8–69.4). Five of 11 evaluable BRCA pts had a confirmed investigator-assessed RECIST/PCWG3 response (45.5%; 95% CI, 16.7–76.6). Overall, the most common treatment-emergent adverse events (TEAEs) included nausea (48.1%; grade ≥3, 3.8%) and asthenia/fatigue (44.2%; grade ≥3, 1.9%). One (1.9%) pt discontinued due to a TEAE; no deaths were reported.
Rucaparib has encouraging antitumour activity in mCRPC pts with a deleterious alteration in BRCA1 or BRCA2. Updated data from current and newly enrolled pts will be presented, including from pts with other gene alterations.
Clinical trial identification
Legal entity responsible for the study
Clovis Oncology, Inc.
Clovis Oncology, Inc.
Writing and editorial support, funded by Clovis Oncology, Inc. (Boulder, CO, USA) was provided by Nathan Yardley, PhD, and Shannon Davis of Ashfield Healthcare Communications (Middletown, CT, USA).
W. Abida: Consulting, Advisory role: Clovis Oncology; Honoraria: Caret Healthcare; Research funding: AstraZeneca, Zenith Epigenetics. N.J. Vogelzang: Consulting, Advisory role: Caris, Sanofi Aventis, Bayer, Pfizer, Janssen, AstraZeneca, Astellas; Stock options owner: Caris; Editor: Up-To-Date. R.J. Amato: Consulting, Advisory role, Speaker bureaus: Jansen, Astellas/Pfizer (Medivation), Novartis. A. Hussain: Consulting, Advisory role: Bayer, Bristol-Myers Squibb, AstraZeneca. A. Patnaik: Consulting, Advisory role: Janssen; Research funding: Bristol-Myers Squibb, GlaxoSmithKline. D. Petrylak: Consulting, Advisory role: Bayer, Bellicum Pharmaceuticals, Dendreon, Johnson & Johnson, Exelixis, Ferring, Millenium, Medivation, Pfizer, Roche, Sanofi and Tyme Pharmaceuticals; Expert testimony: Celgene, Sanofi; Research funding: Oncogenex, Progenics, Johnson & Johnson, Dendreon, Sanofi, Endocyte, Genentech, Merck, Astellas Medivation, Novartis, Agensys, AstraZeneca, Bayer, Lilly, Innocrin Pharma, MedImmune, Millineum, Pfizer, Roche, Sotio; Stock owner, Other ownership interests: Bellicum Pharmaceuticals and Tyme, Inc. C.J. Ryan: Consulting, Advisory role: Bayer, Millennium; Honoraria: Janssen Oncology, Astellas Pharma; Research funding: BIND Biosciences, Karyopharm Therapeutics, Novartis. J. Zhang: Consulting, Advisory role, Speaker’s bureaus: AstraZeneca, Sanofi; Research funding: AstraZeneca, Astellas Pharma, Bayer. A.D. Simmons, D. Despain, M. Collins, T. Golsorskhi: Employee, Stock owner, Stock option owner: Clovis Oncology. H.I. Scher: Consulting, Advisory role: AstraZeneca, Astellas Pharma, Bristol-Myers Squibb, Celgene, Endocyte, Exelixis, Endo Pharmaceuticals, Ferring, Foundation Medicine, Genentech, Janssen, OncologySTAT, Palmetto GBA, Pfizer, Sanofi, Takeda, Ventana Medical Systems, BIRB-Copernicus Group, Medivation; Speaker’s bureau: WebMD; Travel, accommodation: Exelixis, Janssen, Sanofi, Endocyte, AstraZeneca, Genentech, Bristol-Myers Squibb, Celgene, Pfizer, Takeda, Ferring, WIRB-Copernicus Group, and Astellas Pharma; Honoraria: Chugai Pharma; Research funding: BIND Biosciences, Exelixis, Janssen, Medivation, Janssen Diagnostics. S. Chowdhury: Consulting, Advisory role, Speaker’s bureaus: Clovis Oncology, Sanofi, Pfizer, Astellas Pharma, Janssen; Honoraria: GlaxoSmithKline, Novartis; Research funding: Sanofi, Johnson & Johnson. All other authors have declared no conflicts of interest.