Anaplastic Features in Advanced Prostate Cancer With and Without DNA Damage Repair Mutations

Area of Science:

• Oncology
• Genetics
• Clinical Trials

Background:

• Anaplastic prostate cancer presents a poor prognosis and limited therapeutic strategies.
• This study investigates DNA damage repair (DDR) mutations in metastatic castration-resistant prostate cancer (mCRPC) patients treated with durvalumab and olaparib.
• The research aims to identify anaplastic features and their correlation with DDR mutations.

Purpose of the Study:

• To identify anaplastic features in metastatic castration-resistant prostate cancer (mCRPC) patients.
• To determine the prevalence of DNA damage repair (DDR) mutations in patients with and without anaplastic features.
• To examine the association between anaplastic features, DDR mutations, and treatment outcomes with durvalumab and olaparib.

Main Methods:

• A phase II clinical trial involving mCRPC patients previously treated with enzalutamide, abiraterone, or both.
• Patients received durvalumab (1500 mg i.v. every 28 days) and olaparib (300 mg p.o. every 12 hours) until disease progression or toxicity.
• Mandatory baseline biopsies of metastatic lesions were performed for molecular analysis.

Main Results:

• Eleven patients (20%) exhibited anaplastic features; 43 (78.2%) did not.
• DDR mutation rates (germline and somatic) were comparable between anaplastic and nonanaplastic groups.
• Median progression-free survival (PFS) was similar for both groups (6.5 months vs. 5.1 months).

Conclusions:

• Patients with and without anaplastic features demonstrated similar overall rates of DDR mutations.
• A trend towards improved PFS was observed in anaplastic patients receiving olaparib and durvalumab.
• The findings suggest that anaplastic features may not preclude response to PARP inhibitors and immunotherapy in mCRPC.