Phase II trial evaluating olaparib maintenance in patients with metastatic castration resistant prostate cancer (mCRPC) after docetaxel treatment, reaching partial or stable response: SOGUG-IMANOL study.

168 Background: Prostate cancer is the second most common cancer in men. A number of important systemic therapies have been developed to treat mCRPC and now comprise the current therapeutic landscape. Docetaxel became the first systemic therapy to improve survival in these men in a randomized study demonstrating superiority versus mitoxantrone (18.9 months versus 16.5, p=0,004). But, inexorably, after stopping, disease progresses. Methods: A prospective phase II trial was designed to test Olaparib maintenance efficacy, in terms of progression free survival (PFS), in patients with mCRPC with DNA-repair defects that have achieved partial or complete response after being treated with systemic therapy (at least six cycles of docetaxel). Results: 134 mCRPC patients were included since Feb-2018 to Nov-2020 and were tested for DDR alterations. 19.4% of patients had somatic mutations (30.8% BRCA2, 3.8% BRCA1, 19.2% ATM, 7.7% CHEK2, 7.7% PALB2). 53,8% received Olaparib maintenance treatment, with a median follow-up of 23.3 months. Median age was 73 years. Median basal PSA was 17 ng/dL. 100% were metastatic (14.3% de novo and 85.7% relapsed after primary treatment), 78.6% had bone metastasis, 35.7% visceral and 35.7% adenopathies. 42.9% had previous treatment with abiraterone and 35.7% with enzalutamide. 46.2% received at least 8 cycles of docetaxel. 7.1% achieved a partial response and 92.9% a disease stabilization. Response to Olaparib treatment was 14.3% partial response, 71.4% stabilization and 7.1% disease progression.14.3% had a PSA50 decrease. Median duration of response was 8.27 months. Median PFS was 10.1 months. Median PSA-PFS was 3.5 months. G3/4 adverse events were 21.4% asthenia,14.3% anemia and 7.1% neutropenia. Conclusions: Olaparib maintenance after at least six cycles of docetaxel shows promising activity in mCRPC with DDR alterations, with an acceptable toxicity profile. Our pathogenic mutations percentage (19,4%) is in line with previous publications. Clinical trial information: NCT03434158 .