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TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations

  • 0Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.
The Oncologist +

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June 17, 2024

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June 17, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Rucaparib showed clinical responses in metastatic prostate cancer patients with HRR mutations, even without androgen deprivation therapy. However, the study did not meet its efficacy goal, limiting further investigation of this treatment approach.

Area Of Science

  • Oncology
  • Genetics
  • Pharmacology

Background

  • Established efficacy of PARP inhibitors (PARPi) in metastatic castration-resistant prostate cancer with HRR mutations.
  • Hypothesis: PARPi benefit can be maintained without androgen deprivation therapy (ADT) in HRR-mutated prostate cancer.
  • Investigated rucaparib monotherapy in metastatic hormone-sensitive prostate cancer (mHSPC).

Purpose Of The Study

  • To evaluate the efficacy of rucaparib monotherapy in patients with mHSPC and HRR mutations, without concurrent ADT.
  • To determine if PARPi can be effective in this patient population without standard ADT.
  • To assess the primary endpoint of confirmed PSA50 response rate.

Main Methods

  • Phase II, multi-center, single-arm clinical trial (NCT03413995).
  • Enrolled patients with asymptomatic mHSPC and pathogenic germline HRR gene mutations.
  • Administered rucaparib 600 mg orally twice daily without ADT.

Main Results

  • A confirmed PSA50 response rate of 41.7% was observed (5/12 patients), not meeting the pre-specified efficacy threshold.
  • Objective response rate was 60% (3/5 patients) in those with measurable disease, all with BRCA2 mutations.
  • Median radiographic progression-free survival was 12.0 months; adverse events were generally low-grade.

Conclusions

  • Rucaparib monotherapy demonstrated clinical activity in biomarker-selected mHSPC patients without ADT.
  • The study did not meet its primary efficacy endpoint, leading to truncated enrollment.
  • Further research on PARPi without ADT in mHSPC is unlikely to impact clinical practice due to unmet efficacy thresholds.

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