Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2.
For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL).
Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms.
In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.
Cancer. 2024 Jan 01 [Epub ahead of print]
Rana R McKay, Wanling Xie, Xiaoyu Yang, Andres Acosta, Dana Rathkopf, Vincent P Laudone, Glenn J Bubley, David J Einstein, Peter Chang, Andrew A Wagner, Christopher J Kane, Mark A Preston, Kerry Kilbridge, Steven L Chang, Atish D Choudhury, Mark M Pomerantz, Quoc-Dien Trinh, Adam S Kibel, Mary-Ellen Taplin
Department of Medicine, University of California San Diego, La Jolla, California, USA., Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Department of Urology, University of California San Diego, La Jolla, California, USA., Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.