title: Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone.
abstract: Purpose:To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC).Experimental Design:Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment.Results:Forty-six patients enrolled in the AAP-naïve (n= 25) and post-AAP (n= 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months-not reached) and 3.7 months (95% CI, 2.8-5.6 months), and median time on treatment 21 months (range, 2.6-37.5) and 4.9 months (range, 1.3-23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59-93) and 64% (95% CI, 43-82) of AAP-naïve and 43% (95% CI, 22-66) and 10% (95% CI, 1-30) of post-AAP patients remained on treatment for 6+ and 12+ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain.Conclusions:Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer.Clin Cancer Res; 23(14); 3544-51. ©2017 AACR.
authors.affiliation: Sidney Kimmel Center for Prostate and Urologic Cancers, Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York. Rathkopd@mskcc.org.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach, South Carolina.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Shore
authors.affiliation: Chesapeake Urologic Research Associates, Baltimore, Maryland.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Tutrone
authors.affiliation: Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Joshi J
authors.initials: JJ
authors.lastname: Alumkal
authors.affiliation: UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: University of Alabama Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Saleh
authors.affiliation: Nebraska Cancer Specialists, Omaha, Nebraska.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Hauke
authors.affiliation: Janssen Research & Development, Philadelphia, Pennsylvania.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bandekar
authors.affiliation: Aragon Pharmaceuticals, San Diego, California.
authors.forename: Edna Chow
authors.initials: EC
authors.lastname: Maneval
authors.affiliation: Janssen Biologics, B.V., Leiden, the Netherlands.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: de Boer
authors.affiliation: Janssen Research & Development, Los Angeles, California.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Yu
authors.affiliation: Sidney Kimmel Center for Prostate and Urologic Cancers, Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013867:Thiohydantoins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D013867:Thiohydantoins; C572045:apalutamide; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; D011241:Prednisone