Phase 3 TRITON3 Trial Meets Primary End Point of Radiographic PFS With Rucaparib for mCRPC

The primary end point of significantly improved radiographic progression-free survival (rPFS) in the phase 3 TRITON3 trial (NCT02975934) was met when rucaparib (Rubraca) monotherapy was used to treat patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) with BRCA mutations compared with physician’s choice, according to a press release from Clovis Oncology.

Of the 405 patients enrolled on the trial, statistical significance was achieved with regard to rPFS in the rucaparib monotherapy arm (n = 270) vs the control arm (n = 135; HR, 0.61; 95% CI, 0.47-0.80). The median PFS in the rucaparib arm was 10.2 months vs 6.4 months for those in the control arm (P = .0003).

Compared with the control arm, the rucaparib monotherapy arm achieved a statistically significant improvement in radiographic PFS among patients with a BRCA mutation (HR, 0.50; 95% CI, 0.36-0.69). The median PFS for this group was 11.2 months in the rucaparib arm vs 6.4 months in the control arm (P <.0001). The HR for rPFS was 0.97 (95% CI, 0.59-1.52) for patients with an ATM mutation (n = 103). In the rucaparib arm (n = 69), the median radiographic PFS was 8.1 months compared with 6.8 months in control arm (n = 34; nominal P = .8421).

A supplemental new drug application for the single-agent is planned to be submitted to the FDA during the first quarter of 2023.

“We believe that the positive results from TRITON3 further demonstrate the important role that [rucaparib] can play as a treatment option for men with [mCRPC] associated with homologous recombination deficiency, and we look forward to submitting these data to the regulatory authorities in the [United States] during Q1 2023. Not only does this provide a potential treatment option for eligible men with earlier stage disease, but it is the first and only PARP inhibitor that has demonstrated superior [rPFS] compared [with] chemotherapy, which is today the standard of care for these patients,” Patrick J. Mahaffy, president and chief executive officer at Clovis Oncology, said in the press release.

Patients who enrolled on the multicenter, open-label, randomized trial had either a BRCA or ATM mutation. Patients received either rucaparib monotherapy or physician’s choice treatment which included docetaxel, abiraterone acetate, or enzalutamide (Xtandi).

To be enrolled on the trial, patients must have disease progression after treatment with 1 prior next-generation androgen receptor-targeted therapy or a deleterious mutation in BRCA or ATM. Additionally, patients may also receive qualifying androgen receptor-targeted therapy in either the hormone-sensitive or castration-resistant setting following.

At the interim analysis, the secondary end point of overall survival favored the rucaparib arm. However, data are not yet mature.

Grade 3 or higher treatment-emergent adverse effects (TEAEs) in the rucaparib arm included anemia (23.7%), neutropenia (7.4%), asthenia (7.0%), thrombocytopenia (5.9%), and alanine transaminase and aspartate aminotransferase increase (5.2%). In the rucaparib arm, the discontinuation rate was 14.8% due to TEAEs vs 21.5% in the control arm.

“This trial demonstrates the potential for rucaparib to treat men with early-stage [mCRPC],” principal investigator Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy in France, and a full professor of Oncology at the University of Paris-Saclay, concluded. “To my knowledge, this is the first time in two decades that a potential new treatment, rucaparib, has shown in a randomized controlled trial rPFS efficacy over an investigator’s choice control arm that included docetaxel chemotherapy, a long-standing standard of care for men with [mCRPC], and this is excellent news for patients.”

Reference

TRITON3 phase 3 trial Of Rubraca® (Rucaparib) achieves primary endpoint in men with metastatic castration-resistant prostate cancer with BRCA or ATM mutations. News Release. Clovis Oncology. October 3, 2022. Accessed October 3, 2022. https://bit.ly/3SyXsrQ