Alexander Pan1, Rachel E Reingold1,2, Jimmy L Zhao3, Andrea Moy4, Lukas Kraehenbuehl1,5, George Dranitsaris6, Sean M McBride7, Howard I Scher3, Marisa A Kollmeier7, Han Xiao3, Dana E Rathkopf3, Mario E Lacouture1,8. 1. Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 2. Albert Einstein College of Medicine, Bronx, New York. 3. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Dermatopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Parker Institute for Cancer Immunotherapy, Ludwig Collaborative and Swim Across America Laboratory, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Department of Public Health, Falk College, Syracuse University, Syracuse, New York. 7. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Department of Dermatology, Weill Cornell Medical College, New York, New York.
Abstract
PURPOSE: Patients with prostate cancer (PCa) treated with apalutamide frequently develop rash. We aim to characterize apalutamide-related dermatological adverse events (dAEs) and management. MATERIALS AND METHODS: We assessed 303 patients with PCa treated with apalutamide. DAE frequency and time to onset were calculated and clinicopathological features and management described. Associations between dAE occurrence and clinical trial participation, as well as abiraterone/prednisone exposure were detected using logistic regression models. RESULTS: Seventy-one (23.4%) patients had all-grade dAE occurring at a median of 77 (IQR: 30-135) days post-exposure. Twenty (6.6%) dAE-related therapy interruptions included: 8 (2.6%) with dose maintained on rechallenge, 7 (2.3%) with dose reduction and 5 (1.7%) with discontinuation. Common dAEs were maculopapular rashes (33.8%) and xerosis (32.4%). Seven (77.8%) of 9 histological analyses of skin biopsies supported a drug reaction. No significant differences in laboratory hematological, hepatic and renal function were detected between dAE and no dAE cohorts. Most treated grade 1/2 dAEs (29, 40.8%) required topical steroids (14, 19.7%); few required oral steroids (3, 4.2%) ± oral antihistamines. Most grade 3 dAEs (8, 11.3%) required oral/topical steroids (5, 7.0%); few required topical steroids (3, 4.2%) ± oral antihistamines. Clinical trial patients (180, 59.4%) were more likely to report dAEs than those in the off-trial setting (OR=5.1 [95% CI 2.55-10.12]; p <0.001). Of clinical trial patients, concomitant abiraterone/prednisone recipients (109 of 180, 60.6%) were more likely to report dAEs (OR=3.1 [95% CI 1.53-6.17]; p=0.002). CONCLUSIONS: Apalutamide-related dAEs are frequent and can be managed with topical ± oral steroids. With expanded approval of apalutamide, dAE identification and management are essential.
PURPOSE: Patients with prostate cancer (PCa) treated with apalutamide frequently develop rash. We aim to characterize apalutamide-related dermatological adverse events (dAEs) and management. MATERIALS AND METHODS: We assessed 303 patients with PCa treated with apalutamide. DAE frequency and time to onset were calculated and clinicopathological features and management described. Associations between dAE occurrence and clinical trial participation, as well as abiraterone/prednisone exposure were detected using logistic regression models. RESULTS: Seventy-one (23.4%) patients had all-grade dAE occurring at a median of 77 (IQR: 30-135) days post-exposure. Twenty (6.6%) dAE-related therapy interruptions included: 8 (2.6%) with dose maintained on rechallenge, 7 (2.3%) with dose reduction and 5 (1.7%) with discontinuation. Common dAEs were maculopapular rashes (33.8%) and xerosis (32.4%). Seven (77.8%) of 9 histological analyses of skin biopsies supported a drug reaction. No significant differences in laboratory hematological, hepatic and renal function were detected between dAE and no dAE cohorts. Most treated grade 1/2 dAEs (29, 40.8%) required topical steroids (14, 19.7%); few required oral steroids (3, 4.2%) ± oral antihistamines. Most grade 3 dAEs (8, 11.3%) required oral/topical steroids (5, 7.0%); few required topical steroids (3, 4.2%) ± oral antihistamines. Clinical trial patients (180, 59.4%) were more likely to report dAEs than those in the off-trial setting (OR=5.1 [95% CI 2.55-10.12]; p <0.001). Of clinical trial patients, concomitant abiraterone/prednisone recipients (109 of 180, 60.6%) were more likely to report dAEs (OR=3.1 [95% CI 1.53-6.17]; p=0.002). CONCLUSIONS: Apalutamide-related dAEs are frequent and can be managed with topical ± oral steroids. With expanded approval of apalutamide, dAE identification and management are essential.
Entities:
Keywords:
androgen receptor antagonists; apalutamide; dermatology; medical oncology; prostatic neoplasms
Authors: Kim N Chi; Neeraj Agarwal; Anders Bjartell; Byung Ha Chung; Andrea J Pereira de Santana Gomes; Robert Given; Álvaro Juárez Soto; Axel S Merseburger; Mustafa Özgüroğlu; Hirotsugu Uemura; Dingwei Ye; Kris Deprince; Vahid Naini; Jinhui Li; Shinta Cheng; Margaret K Yu; Ke Zhang; Julie S Larsen; Sharon McCarthy; Simon Chowdhury Journal: N Engl J Med Date: 2019-05-31 Impact factor: 91.245
Authors: Nicola J Clegg; John Wongvipat; James D Joseph; Chris Tran; Samedy Ouk; Anna Dilhas; Yu Chen; Kate Grillot; Eric D Bischoff; Ling Cai; Anna Aparicio; Steven Dorow; Vivek Arora; Gang Shao; Jing Qian; Hong Zhao; Guangbin Yang; Chunyan Cao; John Sensintaffar; Teresa Wasielewska; Mark R Herbert; Celine Bonnefous; Beatrice Darimont; Howard I Scher; Peter Smith-Jones; Mark Klang; Nicholas D Smith; Elisa De Stanchina; Nian Wu; Ouathek Ouerfelli; Peter J Rix; Richard A Heyman; Michael E Jung; Charles L Sawyers; Jeffrey H Hager Journal: Cancer Res Date: 2012-01-20 Impact factor: 12.701
Authors: Matthew R Smith; Fred Saad; Simon Chowdhury; Stéphane Oudard; Boris A Hadaschik; Julie N Graff; David Olmos; Paul N Mainwaring; Ji Youl Lee; Hiroji Uemura; Angela Lopez-Gitlitz; Géralyn C Trudel; Byron M Espina; Youyi Shu; Youn C Park; Wayne R Rackoff; Margaret K Yu; Eric J Small Journal: N Engl J Med Date: 2018-02-08 Impact factor: 91.245
Authors: Aurelius Omlin; Oliver Sartor; Christian Rothermundt; Richard Cathomas; Johann S De Bono; Liji Shen; Zhen Su; Silke Gillessen Journal: Clin Genitourin Cancer Date: 2015-01-30 Impact factor: 2.872
Authors: Paul L Nguyen; Shabbir M H Alibhai; Shehzad Basaria; Anthony V D'Amico; Philip W Kantoff; Nancy L Keating; David F Penson; Derek J Rosario; Bertrand Tombal; Matthew R Smith Journal: Eur Urol Date: 2014-08-02 Impact factor: 20.096