Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations

Clin Genitourin Cancer. 2024 Jun;22(3):102080. doi: 10.1016/j.clgc.2024.102080. Epub 2024 Mar 23.

Abstract

Background: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations.

Methods: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014.

Results: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy.

Conclusions: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

Keywords: Cancer genetics; Cancer therapy; Outcomes research; Predictive biomarkers; Urological cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • BRCA2 Protein* / genetics
  • Bridged-Ring Compounds / administration & dosage
  • Bridged-Ring Compounds / therapeutic use
  • Cyclin-Dependent Kinases / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / genetics
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Recombinational DNA Repair*
  • Retrospective Studies
  • Taxoids / administration & dosage
  • Taxoids / therapeutic use
  • Treatment Outcome

Substances

  • BRCA2 Protein
  • CDK12 protein, human
  • ATM protein, human
  • BRCA2 protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Taxoids
  • Cyclin-Dependent Kinases
  • Prostate-Specific Antigen
  • Bridged-Ring Compounds
  • taxane