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A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate Cancer Demonstrating
Kamal Kant Sahu1, Haoran Li2, Vinay Mathew Thomas1
1Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
The Oncologist
|March 7, 2024
Summary
Rucaparib showed promise as a treatment to delay androgen deprivation therapy (ADT) in men with high-risk prostate cancer. This study in patients with BRCAness mutations demonstrated an acceptable safety profile and efficacy signal.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Germline and somatic BRCA mutations are poor prognostic markers in prostate cancer, associated with earlier diagnosis and faster progression to metastatic disease.
- Patients with BRCAness mutations, including alterations in ATM, CHEK2, PALB2, and RAD51, face a higher risk of aggressive disease and poorer survival outcomes.
- The side effects of androgen deprivation therapy (ADT) make delaying its initiation an attractive strategy for younger prostate cancer patients.
Purpose of the Study:
- To assess the efficacy and safety of rucaparib as a potential ADT-sparing approach in patients with biochemically recurrent, nonmetastatic prostate cancer (nmHSPC) and a BRCAness genotype.
- To evaluate the prostate-specific antigen (PSA) progression-free survival (PSA-PFS) as the primary endpoint.
Main Methods:
- A single-arm, open-label, phase II trial involving patients with high-risk biochemically recurrent nmHSPC and a "BRCAness" genotype (PSA doubling time <9 months).
- Patients received oral rucaparib 600 mg twice daily until PSA progression, with a planned 2-year follow-up.
- Primary endpoint: PSA progression-free survival (PSA-PFS). Secondary endpoints: safety, PSA 50% response rate, and undetectable PSA.
Main Results:
- The trial enrolled 7 patients with various pathogenic alterations (ATM, BRCA2, BRCA1, BRIP1, RAD51).
- Median PSA-PFS was 35.37 months (95% CI, 0-85.11 months) with a median follow-up of 18 months.
- Two patients achieved PSA50, with undetectable nadir PSA. Grade ≥3 adverse events were rare (anemia and rash in one patient each).
Conclusions:
- Rucaparib demonstrated an acceptable toxicity profile and an efficacy signal for an ADT-sparing strategy in biochemically recurrent nonmetastatic prostate cancer patients with BRCAness.
- Understanding the optimal role of systemic therapy is challenging due to the rapidly evolving standard of care and the rarity of BRCAness in nonmetastatic hormone-sensitive prostate cancer.
