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- Title
TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations.
- Authors
Markowski, Mark C; Sternberg, Cora N; Wang, Hao; Wang, Tingchang; Linville, Laura; Marshall, Catherine H; Sullivan, Rana; King, Serina; Lotan, Tamara L; Antonarakis, Emmanuel S
- Abstract
Background The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Methods This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate. Results Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected. Conclusion Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.
- Subjects
UNITED States; THERAPEUTIC use of antineoplastic agents; RESEARCH funding; ENZYME inhibitors; CLINICAL trials; PROSTATE tumors; TREATMENT effectiveness; DESCRIPTIVE statistics; TUMOR markers; METASTASIS; INDOLE compounds; DNA repair; RESEARCH; GENETIC mutation; SURVIVAL analysis (Biometry); CONFIDENCE intervals; SEQUENCE analysis
- Publication
Oncologist, 2024, Vol 29, Issue 9, p794
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyae120