Maluf Fernando C, Schutz Fabio A, Cronemberger Eduardo H, Luz Murilo de A, Martins Suelen P S, Muniz David Q B, Bastos Diogo A, Cárcano Flavio M, Smaletz Oren, Soares Andrey, Peixoto Fábio A, Gomes Andrea J, Cruz Felipe M, Franke Fabio A, Herchenhorn Daniel, Dos Santos Telma M, Fabricio Vanessa de C, Gidekel Rosemarie, Werutsky Gustavo, de Jesus Rafaela G, Souza Vinicius C, Fay André P
Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Beneficência Portuguesa de São Paulo, São Paulo, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil.
Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
Eur J Cancer. 2021 Oct 13;158:63-71. doi: 10.1016/j.ejca.2021.08.032.
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.
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.
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.
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.
ClinicalTrials.govNCT02867020.
雄激素剥夺疗法（ADT）联合阿帕鲁胺、醋酸阿比特龙加泼尼松、恩杂鲁胺或多西他赛是晚期去势敏感性前列腺癌（CSPC）的标准治疗方法。我们研究了晚期CSPC的无ADT替代方案。
LACOG 0415是一项2期、开放标签、非对照、随机试验。晚期CSPC患者被随机分组（1:1:1），分别接受戈舍瑞林加醋酸阿比特龙和泼尼松（ADT加AAP组）、阿帕鲁胺（APA组）或阿帕鲁胺加醋酸阿比特龙和泼尼松（APA加AAP组）。主要终点是在意向性分析人群中第25周时PSA≤0.2 ng/mL的患者比例。对所有至少接受一剂研究药物的患者进行安全性分析。
128例随机分组患者中，120例患者在第25周时可评估PSA反应；17.2%有高危生化复发，8.6%有局部晚期疾病，74.2%有远处转移。在第25周时，ADT加AAP组、APA组和APA加AAP组分别有75.6%（95%CI 59.7%-87.6%）、60.0%（95%CI 43.3%-75.1%）和79.5%（95%CI 63.5%-90.7%）的患者PSA≤0.2 ng/mL。PSA下降≥80%的比例分别为100%、90.0%和97.4%。3-4级不良事件分别在31.0%、21.4%和36.4%的患者中观察到。APA组睾酮水平显著升高，ADT加AAP组和APA加AAP组睾酮水平显著降低。
无ADT替代方案在晚期CSPC中可提供较高的PSA反应，尽管APA组在第25周时未达到预期的PSA≤0.2 ng/mL率。这些结果值得进一步研究无ADT治疗作为晚期CSPC替代方案的可能性。
ClinicalTrials.govNCT02867020。
