A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415)

Abstract

Background: Androgen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. Patients and methods: LACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of 0.2 ng/mL at week 25 in the modified intentionto-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. Results: Of 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of 0.2 ng/mL was observed in 75.6% (95%CI 59.7%e87.6%), 60.0% (95%CI 43.3%e75.1%), and 79.5% (95%CI 63.5%e90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of !80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3e4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. Conclusions: ADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of 0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. Source study registration: ClinicalTrials.gov NCT02867020.

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

“…In study LACOG 0415, the patients were divided into goserelin + abiraterone acetate + prednisone group (ADT + AAP group), apalutamide + abiraterone acetate + prednisone group (APA + AAP group) and apalutamide alone group (APA group) ( 24 ). During the 25-week follow-up period, testosterone levels in the APA group continued to rise while the other two groups remained low.…”

The Association Between [68Ga]PSMA PET/CT Response and Biochemical Progression in Patients with High-Risk Prostate Cancer Receiving Neoadjuvant Therapy

“…Pat ients with high-risk prostate cancer (PCa) have a significant risk of biochemical recurrence and distant metastases after radical prostatectomy (RP) (1), despite the standard therapies of externalbeam radiation therapy in combination with long-term androgen deprivation therapy (ADT) and RP plus extended lymph node dissection (2). Though neoadjuvant therapy before RP for patients with high-risk PCa still remains investigational, results from phase II trials have indicated a favorable pathologic response to neoadjuvant ADT combined with new-generation androgen receptor pathway inhibitors (3)(4)(5)(6)(7)(8) or docetaxel chemotherapy (9,10).…”