They hypothesized that simultaneously targeting the tumor and bone compartment yields superior outcomes than targeting either alone. They previously determined the dose and schedule of co-administering Ra-223 + docetaxel in a randomized phase I/IIa trial. The combination appeared to have superior declines in prostate specific antigen (PSA) and bone markers, delayed PSA progression, and was better tolerated (with adjusted dose/schedule) relative to standard docetaxel alone. They are now conducting a phase III study.
DORA is an open-label investigator-initiated phase III study sponsored by Memorial Sloan Kettering Cancer Center and managed by the Prostate Cancer Clinical Trials Consortium. Patients with mCRPC are randomized (1:1) to docetaxel or docetaxel + Ra-223. Pts with ≥2 bone lesions and progression by Prostate Cancer Working Group 3 criteria are eligible. Other key inclusion criteria are an Eastern Cooperative Oncology Group performance status of 0–1 and normal organ function. Key exclusion criteria are: use of anticancer therapy ≤4 weeks before randomization and use of bone-seeking radiopharmaceuticals or chemotherapy in the castration-resistant setting, and bulky visceral metastases (≥3 lung and/or liver or a lesion ≥2 cm in the previous 8 weeks). Pts will receive docetaxel 75 mg/m2 IV q3w for 10 doses with oral prednisone 5 mg b.i.d. or docetaxel 60 mg/m2 IV q3w for 10 doses with oral prednisone 5 mg b.i.d. + Ra-223 55 kBq/kg IV q6w for 6 injections.
The primary endpoint is overall survival. Secondary and exploratory endpoints include: radiographic progression-free survival, symptomatic skeletal event-free survival, safety, markers of bone metabolism, alterations in circulating tumor cells and DNA, detection of androgen-receptor splice variant 7 and changes in automated bone scan index. Enrollment of 738 patients is expected. The study is being conducted in the US and Netherlands, and the results from this phase III trial will be eagerly awaited.
Presented by: Michael Morris, MD Clinical Director, Genitourinary Medical Oncology Service & Prostate Cancer Section Head, Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA. Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA