ASPIRE: A randomized phase III trial of androgen deprivation therapy (ADT) plus apalutamide (A) with or without docetaxel (D) in metastatic castration-sensitive prostate cancer (mCSPC) stratified by tumor suppressor gene alterations (Alliance A032302).
Abstract
TPS290 Background: Landmark randomized trials established the survival benefit of adding D to ADT in mCSPC. Building on this foundation, subsequent trials (PEACE-1 and ARASENS) demonstrated further survival improvements when androgen receptor pathway inhibitors (ARPI) were added to the ADT + D backbone. However, the independent contribution of D within the triplet regimen remains unclear given lack of prospective evaluation. Additionally, tumor suppressor gene (TSG) alterations involving TP53, PTEN, and RB1 are frequently observed in PC and are associated with aggressive biology and poor outcomes, providing an opportunity to enhance prognostic accuracy and optimize selection of candidates for treatment intensification. We hypothesize that adding D to ADT plus A will improve survival compared to ADT + A in mCSPC and stratification by TSG status may identify different treatment effects across molecular subgroups. Methods: ASPIRE is an open-label, two-arm, randomized phase 3 study to assess the benefit of D added to ADT plus A for patients with mCSPC. Eligible patients include those with confirmed adenocarcinoma of the prostate with evidence of distant metastatic disease on conventional imaging and are appropriate to receive D. Patients with metachronous low-volume disease or PSMA-PET only disease are excluded. Candidates must have next-generation sequencing (NGS) results from a CLIA-certified tissue test available for TSG status stratification at registration. Eligible patients will receive ADT plus A (240 mg PO daily) +/- D for up to 6 cycles until progression of disease by PCWG3/RECIST version 1.1 criteria. Prior therapy with ADT (with or without ARPI) initiated within 120 days before registration is permitted. The primary endpoint is overall survival (OS). Secondary endpoints include OS by TSG status; radiographic progression-free survival (rPFS); time to castration resistance; symptomatic skeletal event–free survival; time to worsening of disease-related symptoms (NCCN-FACT FPSI-17); safety and tolerability (CTCAE v5.0); PSA90 response at 6 weeks and 6 months; time to PSA progression; and objective response rate in patients with measurable disease. The study will enroll 1200 patients and is currently actively accruing patients. Clinical trial information: NCT06931340 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Deepak Kilari
Medical College of Wisconsin, Milwaukee, WI
Karla V. Ballman
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Edward Paul Gelmann
Department of Medicine, University of Arizona, Tucson, AZ
Kevin Kayvan Zarrabi
Thomas Jefferson University, Philadelphia, PA
Shiva Baghaie
University of Chicago, Chicago, IL
Christopher Joseph Sumey
Sanford Cancer Center, Sioux Falls, SD
David W. Hillman
Alliance Statistics and Data Center, Mayo Clinic Rochester, Rochester, MN
Alan Haruo Bryce
Mayo Clinic Arizona, Phoenix, AZ
Brent Shane Rose
Department of Ra, La Jolla, CA
Paul Nguyen
Department of Physics, University of Washington 2 , Seattle, Washington 98195,
Robert Bruce Montgomery
University of Washington, Fred Hutchinson Cancer Center, Seattle, WA
Stephanie A. Berg
Department of Medical Oncology Dana‐Farber Cancer Institute Boston Massachusetts USA
Alan Tan
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Heather Jacene
Dana-Farber Cancer Institute, Boston, MA
Ronald C. Chen
University of Kansas Medical Center, Kansas City, KS
Himisha Beltran
Michael J. Morris
Department of Medicine, Memorial Sloan Kettering Cancer Center
Matthew D. Galsky
Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
Jonathan E. Rosenberg
Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA
Rana R. McKay
Department of Medicine, Urology, and Radiation Medicine and Applied Sciences University of California‐San Diego La Jolla California USA