Andrew J Armstrong1, Neal D Shore2, Russell Z Szmulewitz3, Daniel P Petrylak4, Jeffrey Holzbeierlein5, Arnauld Villers6, Arun Azad7, Antonio Alcaraz8, Boris Alekseev9, Taro Iguchi10, Francisco Gomez-Veiga11, Brad Rosbrook12, Ho-Jin Lee13, Gabriel P Haas13, Arnulf Stenzl14. 1. Duke Cancer Institute Center for Prostate & Urologic Cancers, Durham, North Carolina. 2. Carolina Urologic Research Center, Myrtle Beach, South Carolina. 3. The University of Chicago, Chicago, Illinois. 4. Yale Cancer Center, New Haven, Connecticut. 5. The University of Kansas Medical Center, Kansas City, Kansas. 6. University Hospital Centre, Lille University, Lille, France. 7. Monash Health, Melbourne, Victoria, Australia. 8. Hospital Clinic de Barcelona, Barcelona, Spain. 9. Hertzen Moscow Cancer Research Institute, Moscow, Russia. 10. Osaka City University Graduate School of Medicine, Osaka, Japan. 11. Hospital Universitario de Salamanca, GITUR-IBSAL, Salamanca, Spain. 12. Pfizer Inc. , San Diego, California. 13. Astellas Pharma Inc., Northbrook, Illinois. 14. University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.
Abstract
PURPOSE:Enzalutamide plus androgen deprivation therapy has previously been shown to improve clinical outcomes in men with metastatic hormone-sensitive prostate cancer (ARCHES; NCT02677896). Here, we assessed if and how the pattern of metastatic spread impacts efficacy of enzalutamide plus androgen deprivation therapy in men enrolled in ARCHES. MATERIALS AND METHODS:Men with metastatic hormone-sensitive prostate cancer were randomized 1:1 to enzalutamide (160 mg/day) plus androgen deprivation therapy or placebo plus androgen deprivation therapy, stratified by disease volume and prior docetaxel treatment. The primary end point was radiographic progression-free survival. Secondary end points included time to prostate specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event and castration resistance. Post hoc analyses were performed by pattern of metastatic spread based on study entry imaging. RESULTS: Of the overall population with metastases identified at enrollment (1,146), the largest patient subgroups were those with bone metastases only (513) and those with bone plus lymph node metastases (351); there were fewer men with lymph node metastases only (154) and men with visceral±bone or lymph node metastases (128). Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression vs placebo plus androgen deprivation therapy in men with bone metastases only (HR 0.33) and bone plus lymph node metastases (HR 0.31). Similar improvements in secondary end points were also observed in these subgroups. CONCLUSIONS: These findings indicate that treatment with enzalutamide plus androgen deprivation therapy provides improvements in men with bone and/or lymph node metastases but may be less effective in men with visceral patterns of spread.
RCT Entities:
PURPOSE:Enzalutamide plus androgen deprivation therapy has previously been shown to improve clinical outcomes in men with metastatic hormone-sensitive prostate cancer (ARCHES; NCT02677896). Here, we assessed if and how the pattern of metastatic spread impacts efficacy of enzalutamide plus androgen deprivation therapy in men enrolled in ARCHES. MATERIALS AND METHODS:Men with metastatic hormone-sensitive prostate cancer were randomized 1:1 to enzalutamide (160 mg/day) plus androgen deprivation therapy or placebo plus androgen deprivation therapy, stratified by disease volume and prior docetaxel treatment. The primary end point was radiographic progression-free survival. Secondary end points included time to prostate specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event and castration resistance. Post hoc analyses were performed by pattern of metastatic spread based on study entry imaging. RESULTS: Of the overall population with metastases identified at enrollment (1,146), the largest patient subgroups were those with bone metastases only (513) and those with bone plus lymph node metastases (351); there were fewer men with lymph node metastases only (154) and men with visceral±bone or lymph node metastases (128). Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression vs placebo plus androgen deprivation therapy in men with bone metastases only (HR 0.33) and bone plus lymph node metastases (HR 0.31). Similar improvements in secondary end points were also observed in these subgroups. CONCLUSIONS: These findings indicate that treatment with enzalutamide plus androgen deprivation therapy provides improvements in men with bone and/or lymph node metastases but may be less effective in men with visceral patterns of spread.
Authors: Meredith N Freeman; Albert Jang; Jason Zhu; Farhad Sanati; Lakshminarayanan Nandagopal; Deepak Ravindranathan; Arpita Desai; Audrey Phone; Roberto Nussenzveig; Ellen Jaeger; Sydney A Caputo; Vadim S Koshkin; Umang Swami; Arnab Basu; Mehmet A Bilen; Neeraj Agarwal; Oliver Sartor; Earle F Burgess; Pedro C Barata Journal: Oncologist Date: 2022-03-11