Phase II Trial Evaluating Olaparib Maintenance in Patients with Metastatic Castration-Resistant Prostate Cancer Responsive or Stabilized on Docetaxel Treatment: SOGUG-IMANOL Study

SIMPLE SUMMARY: In this study, based on the results of chemotherapy or poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) maintenance in other tumors, we explore whether olaparib, a PARP inhibitor, could be useful in terms of prolonging radiographic progression of the disease in patients with metastatic castration-resistant prostate cancer with specific mutations whose illness had not progressed under treatment with docetaxel—A standard chemotherapy for these patients. In the 14 patients included in this study harboring mutations in homologous recombination genes, olaparib maintenance was an effective option, stabilizing the metastasis and extending the radiographic and clinical progression of the disease with tolerable and manageable adverse events. Overall, the results suggest this alternative could be useful for selected patients. ABSTRACT: The SOGUG-IMANOL trial was a phase 2, uncontrolled, Spanish multicenter study to assess the effect of maintenance treatment with olaparib on radiographic progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who achieved partial or complete response or disease stabilization on docetaxel treatment and had a documented germline/somatic mutation in any of the homologous recombination repair (HRR) genes. Patients received olaparib 300 mg orally twice daily. From the screened population (n = 134), 26 (19.4%) somatic mutations were found, and 14 patients were included in the study. The median radiographic PFS was 11.1 (95%CI, 5.7 to 16.5) months. The median PSA-PFS was 3.5 (95%CI, 1.0 to 6.0) months, and the median clinical PFS was 14.7 (95%CI, 1.8 to 27.5 months). Clinical benefit was observed in 12 patients (85.7%, 95%CI 67.4% to 100%), including two patients with partial response and 10 with stable disease. Six patients reported grade 3–5 adverse events: asthenia (n = 3), anemia (n = 2) and neutropenia (n = 1). In this setting, olaparib has been shown to be an efficacious maintenance treatment in terms of radiographic PFS and clinical benefit, becoming a therapeutic option for some patients harboring an HRR gene mutation and in scenarios where further investigation is needed.