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

Apresentação em tema: "D ISCUSSÃO DE A RTIGO Fernando Pessuti Médico Residente de Oncologia Clínica da UNICAMP Campinas, 15 de outubro de 2019."— Transcrição da apresentação:

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

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3 Funded by Pfizer and Astellas Pharma PROSPER

4 INTRODUÇÃO

5 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.

6 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

7 MÉTODOS

8 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

9 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.

10 RESULTADOS

11 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.

12 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).

13 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.

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15 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

16 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.

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19 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%)

20 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.

21 CONCLUSÕES

22 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

23 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

24 O BRIGADO !!! C LAUDE M ONET, 1875

25 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