Prostate cancer with oligometastatic relapse: Combining stereotactic ablative radiotherapy and durvalumab, a randomized phase II trial (POSTCARD - GETUG-P13).

Abstract

TPS5088 Background: Following Stereotactic Body RadioTherapy (SBRT) targeting prostate cancer (PCa) oligometastasis, a tumor response assessed by PSA decrease is observed in a majority of case. To increase this tumor response, immune targeting agents can be combined with SBRT. We hypothesize that the anti-PDL1 agent Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this multicenter randomized phase II trial, we therefore propose to assess the comparative efficacy of SBRT with or without Durvalumab (MEDI4736) in oligometastatic recurrent hormone sensitive prostate cancer patients. Methods: Patients with PCa were eligible if they had a biochemical recurrence following treatment with curative intent, with a maximum of 5 bone or lymph node metastases, seen only on FCH-PET CT or Ga-PSMA PET CT, not seen on conventional imaging assessments (bone scan or thorax, abdomen and pelvis CT scan). Main exclusion criteria are serum testosterone level < 8.5 nmol/ml, PSA doubling time less than 6 months, lung, brain, liver or other visceral metastases, any prior immune therapy. Patients were randomly assigned (2:1) to either SBRT + Durvalumab, or SBRT alone, with a stratification by investigation center, and number of metastases (1 vs 2-5). Durvalumab (1500 mg/cycle) will be started one month prior to SBRT to be able to evaluate PSA and immune response to the drug. It will be combined with SBRT (3x 9 or 3 x 11 Gy) and then given adjuvantly until progression with a maximum of 12 months. Ninety-six patients will be recruited in 15 centers over a recruitment period of 2.5 years. The primary endpoint is two-year Progression-free survival. Secondary objectives include quality of life, androgen deprivation therapy free survival, prostate cancer specific survival, overall survival, time to first symptomatic event, acute and late toxicity. Patients in both groups will be observed for PSA progression every 3 months after random assignment, with confirming imaging at PSA progression. Clinical trial information: NCT03795207.