JOURNAL READING

Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy

Presented by :Afifah Nur Kartikasari

012.095.821

Adviser : Prof. Dr. dr. H Rifki Muslim Sp. B, Sp. U

Identitas Jurnal

Title• Increased Survival with

Enzalutamide in Prostate Cancer after Chemotherapy

Author• Howard I. Scher, M.D., Karim

Fizazi, M.D., Ph.D., Fred Saad, M.D.,

Publisher •New England Journal of Medicine

Date •September 27 2012

Backgroud

Kanker prostat (androgen dependent) yang awalnya merespon menjadi resisten terhadap terapi yang menurunkan sirkulasi testosteron atau menghambat ikatan androgen pada reseptor androgen

Enzalutamide (sebelumnya disebut MDV3100) bekerja pada jalur sinyal reseptor androgen,yang merupakan pendorong utama pertumbuhan kanker prostat.

Method

3 phase

Double blind

Placebo-controlled trial

Histological or cytologically confirmed diagnosis of prostate cancer

Castrate level of testosterone <50ng/deciliter

Previous treatment with docetaxel

Progressive disease (PCWG2)

Increasing PSA

Radiography confirmed progression with or without a rise in PSA level

INCLUSION CRITERIA

1199 men with castration resistant prostate cancer after chemotherapy

Receive oral Enzalutamide (800) 160mg/daily or Placebo (399)

Primary End Point was overall survival

Phase 1-2 trial enrolling men with castration resistant prostate cancer

Phase 3 trial, evaluate whether enzalutamide would prolong life in men with progresisive prostate cancer after chemotherapy

Secondary End Point

proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more

the soft-tissue response rate

the quality-of-life response rate

the time to PSA progression

radiographic progression-free survival

the time to the first skeletal-related event

308 of 800 patients (39%) died in the enzalutamide group and 212 of 399 patients (53%) died in the placebo group.

Secondary End pointEnzalutamide Placebo p

PSA-level response rate 54% 2% <0,001

soft-tissue response rate 29% 4% <0,001

quality-of-life response 43% 18% <0,001

the time to PSA progression 8,3 month 3,0 month <0,001

radiographic progression-free survival

8,3 month 2,9 month <0,001

the time to the first skeletal-related event

16,7 month 13,3 month <0,001

In this phase 3 study, we found that enzalutamide, an oral androgen-receptor–signaling inhibitor, significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy by a median of 4.8 months and reduced the risk of death from any cause by 37% versus placebo.

DISCUSSION

Enzalutamide Inhibits Multiple Steps in the AR Signaling Pathway

Mukherji D et al. Expert Opin Investig Drugs 2012;21:227-33. Carson C et al. Urology 2003;61:2-7.

Testosterone/DHT Enzalutamide

Conclusion

Enzalutamide significantly prolonged the survival of men with metastatic

castrationresistant prostate cancer after chemotherapy.

CRITICAL APPRAISAL• Judul :

Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy

– Sudah sesuai dengan isi penelitian

– Penulisan judul < 12 kata

Terdiri dari 4 paragraf

Komponen : terdiri dari introduction, methods,results, dan conclusions

Kurang dari 250 kata

ABSTRACT

PICO ANALYSISPatients

• 1199 men with castration-resistant prostate cancer after chemotherapy according to the eastern Cooperative Oncology Group Performance-status score and pain intensity

Intervention • Enzalutamide

Comparison • Placebo

Outcome

• Reduction in the prostate-spesific antigen(PSA) level by 50% or more.

• the soft tissue response rate• The quality of life response rate , the time to PSA

progression, time to first skeletal-related event

Apakah terkumpul sebuah sampel pasien yang jelas dan representatif pada titik awal perjalanan penyakit?

Ya

Apakah pengamatan pasien cukup panjang dan lengkap?

Ya

Apakah kriteria kesudahan yang obyektif diterapkan secara blind?

Ya

•Apakah dilakukan penyesuaian utk faktor prognosis yang penting?•Apakah dilakukan validasi pada kelompok pasien tes set yang independent?

-

CRITICAL APPRAISAL

Apakah bukti tentang aspek prognosis ini valid?

Apakah bukti tentang aspek prognosis yang valid ini penting?

Seberapa besar kemungkinan kesudahan ini terjadi untuk jangka waktu yang lebih panjang?

Ya

Survival time Enzalutamide 18,4 month

Seberapa presisi estimasi prognosis? Ya

CI 95%, 0,53-0,75

P< 0,001

Apakah kita dapat menerapkan bukti tentang aspek prognosis yang valid dan penting ini pada pasien kita?

Apakah pasien dalam penelitian ini mirip/serupa dengan pasien kita?

Ya

Apakah bukti ini mempunyai pengaruh yang penting secara klinis terhadap kesimpulan kita tentang apa yang perlu ditawarkan atau diberitahukan kepada pasien kita

Ya

VALID

DAPAT DITERAPKAN

PENTING

THANK YOU...