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 intention-to-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%-87.6%), 60.0% (95%CI 43.3%-75.1%), and 79.5% (95%CI 63.5%-90.7%) 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 3-4 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.govNCT02867020.

Keywords: Abiraterone; Advanced prostate cancer; Androgen deprivation therapy; Apalutamide; Castration-sensitive prostate cancer; Hormone-sensitive prostate cancer.

Conflict of interest statement

Conflict of interest statement FCM reports honoraria from Astellas Pharma, Bayer Shering Pharma, Bristol-Myers Squibb Brazil, Janssen Oncology, Med Sharp & Dohme; consulting or advisory role: Astellas Pharma, Bayer Shering Pharma, Bristol-Myers Brazil, Janssen Oncology, Merck Sharp & Dohme, & Dohme; research funding: Janssen- Cilag; and travel expenses: Bayer Shering Pharma and Merck Sharp & Dohme. FAS fees speaker: Janssen, Bayer, Astellas, MSD, BMS, and Roche; advisory board: Bayer, Astellas, Janssen, Pfizer, MSD, and BMS; and sponsored research (as principal investigator): Roche, BMS, MSD, Janssen, AstraZeneca. MAL fees speaker: Astellas, Janssen, Sanofi, Bayer; research grant: AMGEN, Ferring, AstraZeneca, ProScan; advisory board: ProScan, Janssen, Astellas; sponsored research: Ferring, Janssen, Bayer, GSK, Active Biotech; travel expenses: Janssen, AstraZeneca, Pfizer, Bayer. DBQM reports grants from Pfizer; personal fees and non-financial support from Janssen, outside the submitted work. DAB reports personal fees and non-financial support from Bayer, grants, personal fees and non-financial support from Janssen; grants, personal fees and non-financial support from Astellas; personal fees and non-financial support from Roche; personal fees and non-financial support from Merck Sharp Dome; personal fees and non-financial support from Bristol Myers Squibb, outside the submitted work. OS reports non-financial support from Janssen, during the conduct of the study. AS reports personal fees from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Lilly, Merck Serono, MSD, Novartis, Pfizer, Pierre Fabre, Roche; non-financial support from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, Merck Serono, MSD, Pfizer, Roche, Sanofi; grants from Bristol-Myers Squibb, outside the submitted work. FMC reports grants from Janssen-Cilag; travel expenses from Janssen-Cilag and Zodiac. TMS reports grants from Janssen during the conduct of the study; other from Janssen employee, other from AMGEN outside the submitted work. VCF reports other from Janssen Pharmaceuticals during the conduct of the study; other from Janssen Pharmaceuticals outside the submitted work. RG reports other from Janssen Pharmaceuticals during the conduct of the study; other from Janssen Pharmaceuticals outside the submitted work. GW reports grants from Janssen-Cilag during the conduct of the study. RGJ reports grants from Janssen-Cilag during the conduct of the study. VCS reports grants from Janssen-Cilag during the conduct of the study; personal fees from Bayer, Janssen-Cilag and Bristol-Myers Squibb; non-financial support from Bayer and Janssen-Cilag outside the submitted work. APF reports personal fees BMS, Roche, Novartis, Janssen, Astellas, Merck, AstraZeneca; non-financial support from BMS, Roche, Janssen, Astellas, Merck, Ipsen, AstraZeneca outside the submitted work. EHC, SPSM, FMC, FAP, AGJ, FAF and DH have nothing to disclose.

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