Phase II Study of an Androgen Receptor Pathway Inhibitor + Atezolizumab + Gonadotropin-Releasing Hormone Analog and Stereotactic Body Radiotherapy in Hormone-Sensitive Metastatic Prostate Cancer

PURPOSE Metastatic androgen pathway modulation–sensitive (mAPMS) prostate cancer is generally immunologically cold. Emerging data suggest radiotherapy and androgen-deprivation therapy (ADT) augment the antitumor immune response to immune checkpoint blockade. We evaluated the efficacy and safety of atezolizumab combined with androgen receptor pathway inhibition (ARPI), ADT, and stereotactic body radiotherapy (SBRT) to the prostate in patients with de novo mAPMS prostate cancer. PATIENTS AND METHODS SAABR was a multicenter phase II trial conducted at two academic centers. Patients with untreated de novo mAPMS prostate cancer received atezolizumab (1,200 mg intravenously every 3 weeks) followed by initiation of ADT and an ARPI, and SBRT to the prostate delivered in five fractions. Treatment continued for up to 2 years. The primary end point was freedom-from-failure at 2 years, defined as the absence of biochemical recurrence, radiographic progression, study withdrawal, or death. RESULTS Twenty-eight patients were enrolled between July 2020 and April 2023 before the study closed early because of safety concerns. The median age was 65 years (IQR, 58-70); 82% had bone metastases and 50% had high-volume disease. At 2 years, 20 (71%) of 28 patients remained failure-free. Biochemical recurrence occurred in four patients (14%), radiographic progression in three (11%), and one patient (4%) discontinued study participation before 2 years. Treatment-related adverse events occurred in 96% of patients, with grade ≥3 events in 46%. Three serious treatment-related adverse events prompted study closure, including two grade 4 colonic perforations and one grade 5 hemophagocytic lymphohistiocytosis. CONCLUSION Maximal hormonal blockade combined with atezolizumab + SBRT to the prostate is associated with significant toxicity and no clear clinical benefit compared with historic controls in de novo mAPMS prostate cancer.