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 point
Enzalutamide 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 ANALYSIS
Patients
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
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