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)

Fernando C Maluf; Fabio A Schutz; Eduardo H Cronemberger; Murilo de A Luz; Suelen P S Martins; David Q B Muniz; Diogo A Bastos; Flavio M Cárcano; Oren Smaletz; Andrey Soares; Fábio A Peixoto; Andrea J Gomes; Felipe M Cruz; Fabio A Franke; Daniel Herchenhorn; Telma M Dos Santos; Vanessa de C Fabricio; Rosemarie Gidekel; Gustavo Werutsky; Rafaela G de Jesus; Vinicius C Souza; André P Fay

doi:10.1016/j.ejca.2021.08.032

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)

Eur J Cancer. 2021 Oct 13:158:63-71. doi: 10.1016/j.ejca.2021.08.032. Online ahead of print.

Authors

Fernando C Maluf¹, Fabio A Schutz², Eduardo H Cronemberger³, Murilo de A Luz⁴, Suelen P S Martins⁵, David Q B Muniz⁶, Diogo A Bastos⁷, Flavio M Cárcano⁸, Oren Smaletz⁹, Andrey Soares¹⁰, Fábio A Peixoto¹¹, Andrea J Gomes¹², Felipe M Cruz¹³, Fabio A Franke¹⁴, Daniel Herchenhorn¹⁵, Telma M Dos Santos¹⁶, Vanessa de C Fabricio¹⁷, Rosemarie Gidekel¹⁷, Gustavo Werutsky¹⁶, Rafaela G de Jesus¹⁶, Vinicius C Souza¹⁸, André P Fay¹⁹

Affiliations

¹ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Beneficência Portuguesa de São Paulo, São Paulo, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil. Electronic address: maluffc@uol.com.br.
² Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
³ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Centro Regional Integrado de Oncologia, Fortaleza, Brazil.
⁴ Hospital Erasto Gaertner, Curitiba, Brazil.
⁵ Cepho-FMABC, Santo André, Brazil.
⁶ Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil.
⁷ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil.
⁸ Hospital de Câncer de Barretos, Barretos, Brazil.
⁹ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil.
¹⁰ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil; Centro Paulista de Oncologia - Oncoclinicas, São Paulo, Brazil.
¹¹ Instituto COI de Educação, Pesquisa e Gestão em Saúde, Rio de Janeiro, Brazil.
¹² Liga Norte Riograndense Contra o Câncer, Natal, Brazil.
¹³ IBCC Oncologia - Centro Universitário São Camilo, São Paulo, Brazil.
¹⁴ Oncosite - Centro de Pesquisa Clínica, Ijuí, Brazil.
¹⁵ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Oncologia D'OR/Instituto D'OR de Ensino e Pesquisa, Rio de Janeiro, Brazil.
¹⁶ Latin American Cooperative Oncology Group, Porto Alegre, Brazil.
¹⁷ Janssen Pharmaceuticals, Argentina.
¹⁸ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Oncologia D'OR, Salvador, Brazil.
¹⁹ Latin American Cooperative Oncology Group, Porto Alegre, Brazil; PUCRS School of Medicine, Porto Alegre, Brazil; Grupo Oncoclínicas, Porto Alegre, Brazil.

PMID: 34655838
DOI: 10.1016/j.ejca.2021.08.032

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.

Associated data

ClinicalTrials.gov/NCT02867020