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ASCO 2021

ASCO 2021: Phase III study of local or systemic therapy INtensification DIrected by PET in prostate CAncer patients with post-prostaTEctomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191

(UroToday.com) Radiation therapy to the prostate bed and pelvic nodes with short-term androgen deprivation therapy is considered a standard of care salvage therapy paradigm for prostate cancer patients with post-prostatectomy biochemical recurrence. Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases not identified with conventional imaging. Given PET's greater sensitivity and specificity, its findings are increasingly but variably applied to justify modification or omission of standard of care therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of the otherwise non-tailored standard of care approach. Improved systemic control and disease detection with molecular imaging have led to increasing use of focally ablative metastasis-directed radiotherapy, to delay or enhance systemic therapy through increased local control. There is also interest in earlier use of systemic therapy; apalutamide is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer. At the 2021 ASCO virtual annual meeting Dr. Neha Vapiwala and colleagues presented the trial design of INDICATE, a study that will evaluate whether patients with PET-detected lesions benefit from such local or systemic treatment intensification approaches.

Prostate cancer patients with post-radical prostatectomy biochemical recurrent (PSA > 0.5ng/mL; > 0.2ng/mL if within 12 months of radical prostatectomy) and no metastases on conventional imaging who are candidates for standard of care salvage therapy (radiotherapy to prostate bed and pelvic nodes with short-term androgen deprivation therapy) are eligible. Prior to study registration, patients must undergo standard of care baseline PET (18F-fluciclovine but PSMA radiotracers permitted pending commercial availability). Based on institutional clinical interpretation of the standard of care PET, patients will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to standard of care salvage therapy +/- apalutamide for 6 months and Cohort 2 will be randomized to standard of care salvage therapy and apalutamide +/- metastasis-directed radiotherapy to PET-positive lesions.

The trial schema for INDICATE is as follows:

ASCO2021_Vapiwala_INDICATE_1.png

The primary endpoint is PFS, defined as time from randomization to radiographic progression on conventional imaging, symptomatic disease or death. Primary objectives are to evaluate whether addition of apalutamide to standard of care salvage therapy and addition of metastasis-directed radiotherapy to standard of care salvage therapy and apalutamide could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 patients will be randomized with 85% power to distinguish 5-year PFS rate of 90% (apalutamide arm) versus 80% (standard of care arm) using one-sided stratified log-rank test with type I error of 0.025. For Cohort 2, 324 patients will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. This trial is currently actively recruiting patients.

Clinical trial information: NCT04423211


Presented by: Neha Vapiwala, MD, FACR, Professor and Vice-Chair of Education in the Department of Radiation Oncology at University of Pennsylvania, Philadelphia, PA

Co-Authors: Yu-Hui Chen, Steve Y. Cho, Fenghai Duan, Christos Kyriakopoulos, Daniel H. Shevrin, Rana R. McKay, Bridget F. Koontz, Evan Y. Yu, Volkan Beylergil, David A. Mankoff, Jonathan McConathy, Glenn Liu, Terence Z. Wong, Michael Anthony Carducci; University of Pennsylvania, Philadelphia, PA; Dana-Farber Cancer Institute, Boston, MA; University of Wisconsin SMPH, Department of Radiology, University of Wisconsin Carbone Cancer Center, Madison, WI; Brown University, Providence, RI; University of Wisconsin Carbone Cancer Center, Madison, WI; NorthShore University Health System, Evanston, IL; University of California San Diego, Moores Cancer Center, La Jolla, CA; Duke University Medical Center, Durham, NC; Division of Oncology, Department of Medicine, University of Washington, Seattle, WA; Columbia, New York, NY; University of Alabama at Birmingham, Birmingham, AL; Chief, Division of Nuclear Medicine and Radiotheranostics Professor of Radiology Professor in Medicine, Division of Medical Oncology Duke Cancer Institute Medical Physics Graduate Program Duke University Medical Center, Durham, NC; Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD