J O U R N A L R E A D I N G

INCREASED SURVIVAL WITH

ENZALUTAMIDE IN PROSTATE
CANCER AFTER CHEMOTHERAPY

R I F DA H A L I F M AWA D DA H
30101407305

P E M B I M B I N G : D R . H . B A M B A N G S U G E N G , S P. B
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., Mary-Ellen Taplin, M.D., Cora N. Sternberg,
M.D., Kurt Miller, M.D., Ronald de Wit, M.D., Peter Mulders, M.D., Ph.D., Kim N. Chi, M.D., Neal D. Shore,
M.D., Andrew J. Armstrong, M.D., Thomas W. Flaig, M.D., Aude Fléchon, M.D., Ph.D., Paul Mainwaring, M.D.,
Mark Fleming, M.D., John D. Hainsworth, M.D., Mohammad Hirmand, M.D., Bryan Selby, M.S., Lynn Seely,
M.D., and Johann S. de Bono, M.B., Ch.B., Ph.D., for the AFFIRM Investigators*

Publisher

• New England Journal of Medicine

Date

• 27 September 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

Placebo-
Double
3 phase controlled
blind trial
Histological or cytologically confirmed diagnosis of
prostate cancer

Castrate level of testosterone <50ng/deciliter

Previous treatment with docetaxel

INCLUSION
CRITERIA
Progressive disease (PCWG2)

Increasing PSA

Radiography confirmed progression with or

without a rise in PSA level
Phase 1-2 trial enrolling men with castration
resistant prostate cancer

1199 men with castration resistant prostate

cancer after chemotherapy
Phase 3 trial, evaluate whether enzalutamide would
prolong life in men with progresisive prostate cancer
after chemotherapy
Receive oral Enzalutamide (800) 160mg/daily
or Placebo (399)

Primary End Point was overall survival

 Secondary End Point

proportion of patients with a reduction in the prostate-specific

antigen (PSA) level by 50% or more

radiographic progression-free
the soft-tissue response rate
survival

the time to the first skeletal-

the quality-of-life response rate
related event

the time to PSA progression

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 value

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

survival
the time to the first skeletal- 16,7 month 13,3 month <0,001
related event
ENZALUTA
-MIDE
IN
PROSTATE
CANCER
 DISCUSSION
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.
 ENZALUTAMIDE INHIBITS MULTIPLE STEPS
IN THE AR SIGNALING PATHWAY
Testosterone/DHT Enzalutamide

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

Enzalutamide significantly
prolonged the survival of men
with metastatic
castrationresistant prostate
cancer after chemotherapy.
 CRITICAL
APPRAIS AL
 CRITICAL APPRAISAL
• Judul :

Increased Survival with Enzalutamide in Prostate Cancer

after Chemotherapy

Sudah sesuai dengan isi penelitian

Penulisan judul < 12 kata

ABSTRACT

Terdiri dari 4 paragraf

Komponen : terdiri dari introduction, methods,results,

dan conclusions

Kurang dari 250 kata

PICO ANALYSIS
• 1199 men with castration-resistant prostate
Patients
cancer after chemotherapy according to the
eastern Cooperative Oncology Group
Performance-status score and pain intensity
Intervention • Enzalutamide
Comparison • Placebo
• Reduction in the prostate-spesific antigen(PSA)
level by 50% or more.
Outcome • the soft tissue response rate
• The quality of life response rate , the time to PSA
progression, time to first skeletal-related event
 CRITICAL APPRAISAL

Apakah bukti tentang aspek prognosis ini valid?

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

Apakah pengamatan pasien cukup panjang dan lengkap? Ya

Apakah kriteria kesudahan yang obyektif diterapkan secara Ya

blind?
•Apakah dilakukan penyesuaian utk faktor prognosis yang -
penting?
•Apakah dilakukan validasi pada kelompok pasien tes set
yang independent?
APAKAH BUKTI TENTANG ASPEK PROGNOSIS YANG
VALID INI PENTING?

Seberapa besar kemungkinan kesudahan ini terjadi Ya

untuk jangka waktu yang lebih panjang?
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 Ya

pasien kita?

Apakah bukti ini mempunyai pengaruh yang penting Ya

secara klinis terhadap kesimpulan kita tentang apa yang
perlu ditawarkan atau diberitahukan kepada pasien kita
VALID

PENTING

DAPAT DITERAPKAN
TERAPI
Survival Death
long life

Ezalutamide 488 312

Placebo 188 211

 Relative Absolute Number
BENEFIT Risk Risk Need to
Reduction Reduction Treat
(RRR ) (ARR) (NNT)

CER EER (CER-EER): CER-EER 1/ARR

CER

0,47 0,61 29,8% 0,14 7,1