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Findings from the phase 2 TRITON2 trial, which led to the FDA approval of the PARP inhibitor rucaparib in metastatic castration-resistant prostate cancer, have been published in the Journal of Clinical Oncology.
The pivotal findings from the phase 2 TRITON2 trial, which led to the FDA approval of rucaparib (Rubraca) in BRCA-positive metastatic castration-resistant prostate cancer (mCRPC), have now been published online in the Journal of Clinical Oncology.1
In the study, the PARP inhibitor induced a confirmed objective response rate (ORR) per independent review of 43.5% in heavily pretreated patients with mCRPC and a deleterious BRCA alteration. The ORRs were similar, regardless of whether patients had germline or somatic alterations, or whether the alteration was BRCA1 or BRCA2. The investigators did report, however, that PSA response rate was higher among patients with BRCA2 alterations.
Based on the TRITON2 data, the FDA approved rucaparib in May 2020 for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)–associated metastatic mCRPC who have been treated with androgen receptor (AR)–directed therapy and a taxane-based chemotherapy.
“PARP inhibitors have been a welcome additional treatment option available for eligible mCRPC patients, and I’m pleased that this publication provides additional detail about the potential clinical benefit of Rubraca for patients,” Wassim Abida, MD, PhD, principal investigator for the TRITON2 study and a medical oncologist at Memorial Sloan Kettering Cancer Center, stated in a press release.2 “These additional data presented in this publication provide physicians important information to inform treatment decisions for their eligible patients.”
The open-label, multicenter, international TRITON2 study, enrolled male patients with mCRPC associated with 1 of 13 homologous recombination repair gene alterations. Patients had disease progression on androgen receptor (AR)–directed therapy and 1 prior taxane-based chemotherapy.
Overall, the efficacy and safety populations for TRITON2 included 115 BRCA-positive patients with or without measurable disease. The median patient age was 72 (range, 50-88), 74% of patients were white, and all except 2 patients had an ECOG performance status <2. The median baseline PSA was 61.1 ng/mL and 67% of patients had a Gleason score ≥8 at baseline. Across the population, 62 patients had measurable disease at baseline and 53 patients had nonmeasurable disease.
Prior AR–directed therapy included abiraterone acetate (Zytiga; 64.3%), enzalutamide (Xtandi; 71.3%), and apalutamide (Erleada; 2.6%). Overall, 36.5% of patients had received ≥2 AR-directed therapies. Regarding docetaxel, 14.8% had received the chemotherapy for castration-sensitive disease and 93.9% had received it for castration-resistant disease. Other prior therapies received included cabazitaxel (Jevtana; 7%), sipuleucel-T (Provenge; 10.4%), and radium-223 (Xofigo; 12.2%).
Patients were treated with rucaparib at 600 mg twice daily until radiographic progression or treatment discontinuation. Tumors were radiographically assessed every 8 weeks for 24 weeks, and then every 12 weeks. PSA assessments were performed every 4 weeks.
Twenty-seven (43.5%) of the 62 patients with measurable disease had confirmed ORRs per independent radiology review. The responses comprised 7 complete responses and 20 partial responses. Fifteen of the 27 responders had a duration of response ≥6 months. An additional 28 (45.2%) patients had stable disease, 6 had progressive disease, and 1 patient was not evaluable. Among all 115 patients, the confirmed PSA response rate was 54.8% (n = 63).
Regarding safety, 70 (60.9%) of the 115 patients experienced a grade ≥3 treatment-related adverse event (TEAE). The most common grade ≥3 TEAE was anemia/decreased hemoglobin (25.2%). TEAEs led to dose interruptions or reductions in 63.5% of patients, and discontinuations in 7.8% of patients. There was 1 patient TEAE-related death (acute respiratory distress syndrome)
"There is a critical need for personalized medicines to effectively treat advanced prostate cancer," Akash Patnaik, MD, PhD, a TRITON2 study author and a national authority on prostate cancer research at the University of Chicago Medicine, stated in a press release.3 "Approximately 12% of advanced prostate cancer patients have tumors that harbor a BRCA1 or BRCA2 alteration. We have arrived at an exciting inflection point in the field, as we now have the first FDA approved targeted therapy that can effectively treat a genetically defined subset of mCRPC patients, with poor prognosis and worse clinical outcomes on conventional treatments."
1. Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration [published online August 14, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.01035
2. Journal Of Clinical Oncology Publishes Additional Data From Clovis Oncology’s TRITON2 Clinical Trial Evaluating Rubraca® (Rucaparib) For The Treatment Of MCRPC In Patients With BRCA1/2 Gene Mutations. Published online August 17, 2020. https://bit.ly/3iLmz8v. Accessed August 17, 2020
3. PARP inhibitor becomes new treatment option for some men with advanced prostate cancer Published online August 17, 2020. https://bit.ly/315pWBi. Accessed August 17, 2020