D ISCUSSÃO DE A RTIGO Fernando Pessuti Médico Residente de Oncologia Clínica da UNICAMP Campinas, 15 de outubro de 2019

Funded by Pfizer and Astellas Pharma PROSPER

INTRODUÇÃO

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. The median bone metastasis–free survival among men with nonmetastatic, castration-resistant prostate cancer ranges from 25 to 30 months. The risk of metastases is associated with an increasing PSA level and a PSA doubling time of 10 months or less. Metastatic, castration resistant prostate cancer is fatal, with a median survival of approximately 3 years.

INTRODUÇÃO Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. Enzalutamide: Binds to the androgen receptor and inhibits the binding of androgens Androgen-receptor nuclear translocation Androgen-receptor– mediated DNA binding We hypothesized that enzalutamide: Delay the development of metastases Prostate cancer Castration-resistant Nonmetastatic Rapid PSA doubling time

MÉTODOS

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. Trial Participants Prostate adenocarcinoma Without neuroendocrine differentiation, signet-cell features, or small-cell Rising PSA level despite castration-associated testosterone levels Have been receiving androgen-deprivation therapy Bilateral orchiectomy

MÉTODOS Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. Trial End Points Primary end point : Metastasis-free survival Death Secondary end points : Time to PSA progression PSA response rate (on the basis of a decrease from baseline of ≥50%) Time to the first use of a subsequent antineoplastic therapy Quality-of life Overall survival Safety.

RESULTADOS

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.

RESULTADOS Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. Primary End Point The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group, with a median follow-up of 18.5 months and 15.1 months, respectively. Enzalutamide treatment resulted in a 71% lower risk of radiographic progression or death than did placebo (hazard ratio, 0.29; 95% CI, 0.24 to 0.35; P<0.001) (Fig. 1 and Table 2).

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.

RESULTADOS Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. Secondary End Points Enzalutamide treatment was superior to placebo: Time to PSA progression Time to the first use of a subsequent antineoplastic therapy

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.

RESULTADOS Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. The most common adverse event in patients receiving enzalutamide was fatigue Hypertension (in 12% vs. 5%) Major adverse cardiovascular events (in 5% vs. 3%)

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.

CONCLUSÕES

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA value, enzalutamide treatment resulted in a significant delay : Development of metastases ( 71% lower) Time to PSA progression Time to the first use of a subsequent antineoplastic therapy

CONCLUSÕES Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. No difference: Quality of life Adverse events were more common with enzalutamide * Cardiovascular events + fatigue

O BRIGADO !!! C LAUDE M ONET, 1875

1. Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration- resistant prostate cancer. N Engl J Med. 2018;378:2465–74. REFERÊNCIA BIBLIOGRÁFICA