A phase II, open-label study of durvalumab in combination with stereotactic body radiotherapy in androgen-intact patients with oligometastatic prostate cancer.

Abstract

TPS263 Background: With the introduction of Ga68-PSMA PET, a new cohort of androgen-intact men with oligometastatic prostate cancer (PCa) recurrence has been identified. These men have normal traditional imaging and a disease-free interval usually measured in years from their definitive treatment. Recent data supports the use of metastasis-directed stereotactic body radiotherapy (SBRT) in oligometastatic PCa. Based on our institutional data in 57 patients treated with SBRT alone in the PSMA era, the median PSA progression free survival (PFS) is 11 months. Despite 100% local control, 80% relapsed by 18 months. Improving the PFS for these men is an important clinical need. Achieving this without the introduction of androgen deprivation therapy (ADT) will likely improve quality of life and minimise the adverse consequences of androgen deprivation. Radiotherapy results in cell stress and release of damage associated molecular patterns (DAMPs) with activation of antigen presenting cells. This stimulates a tumour antigen specific T-cell response and abscopal effect which can be heightened with PD-(L)1 inhibition. Most PD-(L)1 inhibition trials in PCa are in men with a high burden of castrate resistant disease. However, data suggests the castrate state can impair host anti-tumour immune response. PD-(L)1 inhibition combined with SBRT in androgen-intact men may result in improved PFS compared with our historical cohort treated with SBRT alone. Methods: This is a non-randomized, open label, phase II study of durvalumab (1500 mg IV every 4 weeks) starting 1 month prior to SBRT in men with recurrent PCa not immediately requiring ADT and with Ga68-PSMA PET detected oligometastasis. SBRT will be delivered with 30Gy/3# to lymph nodes or 24Gy/2# to bone metastasis. Durvalumab will be continued to a maximum of 12 months. Primary outcomes will be freedom from biochemical failure and toxicity. Secondary objectives include biochemical response rate, magnitude of response, overall survival, time and response to subsequent treatments and quality of life. The study is recruiting at Royal North Shore Hospital in Sydney with 18 of the planned 30 patients enrolled. Clinical trial information: ACTRN12619000097145.