Rucaparib extends PFS in advanced prostate cancer
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A randomized phase 3 trial that assessed rucaparib for certain men with advanced prostate cancer met its primary endpoint of improved PFS, according to topline data released by the agent’s manufacturer.
Rucaparib (Rubraca, Clovis Oncology) is an oral, small molecule poly(ADP-ribose) polymerase (PARP) inhibitor. It is approved in the United States for maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
The multicenter, open-label TRITON3 trial included 405 men with chemotherapy-naive metastatic castration-resistant prostate cancer with BRCA or ATM mutations. All men had disease progression after one prior next-generation androgen receptor-targeted therapy.
Researchers assigned 270 men to rucaparib monotherapy. The other 135 received physician’s choice of docetaxel, abiraterone acetate (Zytiga, Janssen) or enzalutamide (Xtandi; Astellas, Pfizer). More than half (55%) of men in the control group received docetaxel.
The study met its primary endpoint, showing improvement in median radiographic PFS per independent radiology review with rucaparib among the intention-to-treat population (10.2 months vs. 6.4 months; HR = 0.61; 95% CI, 0.47-0.8) and among the subgroup of men with BRCA mutations (11.2 months vs. 6.4 months; HR = 0.5; 95% CI, 0.36-0.69).
An exploratory analysis showed no statistically significant PFS benefit among men with ATM mutations (median, 8.1 months vs. 6.8 months; HR = 0.97; 95% CI, 0.59-1.52).
OS data for the intention-to-treat population and the subgroup of men with BRCA mutations had not matured but results favored rucaparib. OS data for the subgroup of men with ATM mutations had matured and favored the control regimen.
Researchers observed no new safety signals with rucaparib during the trial.
The most common treatment-emergent grade 3 or higher adverse events among all rucaparib-treated patients in TRITON3 included anemia (23.7%), neutropenia (7.4%), fatigue (7%), thrombocytopenia (5.9%), and increased alanine aminotransferase or aspartate aminotransferase levels (5.2%).
A lower percentage of men assigned rucaparib than the control regimen discontinued treatment due to treatment-emergent adverse events (14.8% vs. 21.5%).
“Men with this type of metastatic prostate cancer want to get their genetically targeted therapy as early as possible, and this trial clearly shows the value of rucaparib as a treatment for these men,” Alan H. Bryce, MD, chair of the division of hematology and medical oncology at Mayo Clinic in Arizona and principal investigator of the TRITON3 trial, said in a Clovis Oncology-issued press release. “A key point is that rucaparib can replace chemotherapy in this setting. The current standard of care for these men is chemotherapy with docetaxel, and rucaparib is the only PARP inhibitor which has beaten a docetaxel-containing control arm in a clinical trial.”
Complete results from TRITON3 will be submitted for presentation at a medical meeting in early 2023.
Clovis Oncology intends to submit a supplemental new drug application to the FDA seeking approval of rucaparib for the BRCA mutation-positive subgroup. Company officials also will discuss submitting an application for the broader intention-to-treat population.
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