964TiP - ARN-509 in Men with metastatic castration-resistant prostate cancer (CRPC)
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC: 1) non-metastatic treatment-naïve CRPC; 2) mCRPC treatment-naïve (tx-naïve); and 3) mCRPC abiraterone acetate pre-treated (AA). Preliminary results for the 2 cohorts of patients with metastatic CRPC are presented here.
Methods: All patients had metastatic CRPC with progressive disease based on rising PSA and/or imaging. No prior chemotherapy for metastatic prostate cancer was allowed. Patients on the AA pre-treated cohort had to have been treated with AA for at least 6 months. All patients received ARN-509 at the recommended Phase II dose of 240 mg/day (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria in each of the treatment groups. Secondary endpoints included safety, time to PSA progression and objective response rates. PSA assessments were collected every 4 weeks and tumor imaging was performed every 16 weeks.
Results: To date, 32 patients have been enrolled: 25 on the tx-naïve and 7 on the post-AA cohorts, respectively. The combined median age was 67 (range 51-91) and at baseline, patients presented with ECOG performance status 0 (55%), Gleason Score 8-10 (54%), and median PSA of 14.7 (tx-naïve) and 69.6 (post-AA) ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 16 weeks, 4 patients discontinued the study due to disease progression, 2 in each cohort. The most common treatment-related adverse events (AE) were abdominal pain (36%), diarrhea (19%), nausea (16%) and fatigue (10%). There was only 1 treatment-related Grade 3 AE of abdominal pain. At 12 weeks, the PSA response was 91% (tx-naïve) and 60% (post-AA), respectively.
Conclusion: In men with CRPC, ARN-509 is safe and well tolerated with promising preliminary activity in metastatic, chemo-naïve patients both before and after treatment with abiraterone.
Publication (Name of Journal)
Annals of Oncology
DOI
https://doi.org/10.1016/S0923-7534(20)33527-4
Recommended Citation
Rathkopf, D.,
Antonarakis, E.,
Shore, N.,
Tutrone, R.,
Alumkal, J.,
Ryan, C.,
Saleh, M.,
Hauke, R.,
Chow-Maneval, E.,
Scher, H.
(2012). 964TiP - ARN-509 in Men with metastatic castration-resistant prostate cancer (CRPC). Annals of Oncology, 23(9), 1-1.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/90
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This work was published before the author joined Aga Khan University.