NEAR trial: A single-arm phase II trial of neoadjuvant apalutamide monotherapy and radical prostatectomy in intermediate- and high-risk prostate cancer

Author:

Lee Lui Shiong,Sim Adelene Y. L.,Ong Chee Wee,Yang Xinyan,Ng Cedric C. Y.,Liu Wei,Rajasegaran Vikneswari,Lim Abner M. S.,Aslim Edwin JonathanORCID,Ngo Nye-ThaneORCID,Khor Li-Yan,Kanesvaran Ravindran,Allen John Carson Jr,Tay Kae JackORCID,Yuen John Shyi Peng,Chong Tsung Wen,Ho Sun Sien Henry,Teh Bin Tean,Chua Melvin L. K.ORCID

Abstract

Abstract Objective Treatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial is a single-arm, phase II investigation of neoadjuvant apalutamide monotherapy and radical prostatectomy (RP) in the treatment of D’Amico intermediate- and high-risk prostate cancer (NCT03124433). Materials and methods Patients with histologically-proven, D’Amico intermediate- to high-risk prostate adenocarcinoma received apalutamide 240 mg once-daily for 12 weeks followed by RP + /−lymphadenectomy. Primary outcome was pathological complete response (pCR) rate. Secondary outcomes included rate of biochemical response (defined by PSA < 0.03 ng/mL at week 24 from starting apalutamide without subsequent PSA relapse), treatment-related adverse events, and RP complication rates. Correlative biomarker analyses were performed to examine for molecular predictors of treatment responses. Results From 2017 to 2019, 30 patients were recruited, of which 20 and 10 were high and intermediate risk, respectively; 25 completed treatment as per-protocol. We did not observe any pCR on trial; median reduction of cancer burden was 41.7% (IQR: 33.3%–60.0%). 18 out of 25 patients were classified as having a biochemical response (4 did not achieve PSA of <0.03 ng/mL at week 24 and 3 developed PSA relapse subsequently). Dry skin (N = 16; 53.3%), fatigue (N = 10; 33.3%) and skin rash (N = 9; 30.0%) were the most common adverse events, and there was no major peri-operative complication. We observed an association between tumours of low androgen receptor activity and PAM50 basal status with biochemical non-responders, albeit these molecular phenotypes were not associated with pathological response. Conclusions A 12-week course of neoadjuvant apalutamide prior to RP did not meet the primary endpoint of pCR in this trial. Tumours with low androgen receptor activity or of the PAM50 basal subtype may have a reduced response to apalutamide.

Funder

MOH | National Medical Research Council

National Research Foundation Singapore

Ministry of Education - Singapore

National Cancer Centre of Singapore

Duke-NUS Medical School

Sengkang General Hospital

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Urology,Oncology

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