Table C28

KQ1 Outcome IV. Survival: Epoetin versus Control

study authorrandomevalmethodfollow upevents EPO (n/N), reported are deaths if not stated otherwiseevents control (n/N), reported are deaths if not stated otherwiseHR (95% CI)Comments
Littlewood 2001
Littlewood 2001, Martin et al 2003375375Kaplan-Meier, unadjusted, p=0.1326 months median fu, 12 months after last subject completed study155/251 (62%)82/124 (66%)HR 0.81 (0.62; 1.06)lost to follow up: Epo 2, placebo 1
Littlewood 2001 375375Cox- regression, adjusted, p=0.05226 months median fu, 12 months after last subject completed study155/25182/124HR 1.309 in favor of EPO, equivalent to HR 0.76 (0.58; 1.00)calculated by GS
Littlewood 2001 median survival17 months11 months
Information submitted by OrthoBiotech for Cochrane ReviewNRNRCox model, adjusted, p=0.0296Nov 15 1998, 3 months after last subject completed studyNRNRHR 1.38
Information submitted by OrthoBiotech for Cochrane Review375375log rank test p=0.128 (unadjusted)Aug 15 1999; 12 months after last subject completed study155/25182/124NR
Information submitted by J&J for FDA/ODAC hearing375375proportions alive at12 months60%40%HR 1.309, p=0.052, in favor of EPO
Information submitted by J&J for FDA/ODAC hearing375375Hazard ratiodouble-blind study phase plus 30 days41/25122/124HR 0.81 (0.48; 1.36)
Information submitted by J&J for FDA/ODAC hearing375375median survival17 months11 months
Machtay 2004
Abstract publication 20041351351-yr actuarial overall survival1-year70% (assume survival)81% (assume survival)HR 1.57 (0.76; 3.27)
Abstract publication 2004, additional slides148141deaths within 90 days post study< 1 year9/716/70p=0.59
Abstract publication 2004, additional slides1481412- yr overall survivalmedian f/u 14.5 months, for surviving patients 19.4 months27/71 deaths21/70 deathsHR 1.41 (0.8; 2.5), p=0.23
FDA report 2004 135117NR8.7 monthsAt the interim analysis (at 8.7 months) 22 out of 117 patients had died. The analysis showed no statistically significant differences, but non- significant trends towards lower survival in the epoetin alfa arm.
Information submitted by J&J for FDA/ODAC hearing135135ProportionNR17/67 (25%)12/68 (18%)NR
Leyland – Jones 2003
Leyland – Jones 2003 939939Proportion4 months4116NR
Leyland – Jones 2003 939939Proportion, p=0.011712 months70% (survival)76% (survival)NR
FDA report and information submitted by J&J for FDA/ODAC hearing939939Proportion4 months41/46916/470NR
FDA report and information submitted by J&J for FDA/ODAC hearing939939Cox adjusted for metastatic category (ITT)12 months148/469115/470HR 1.37 (1.07; 1,74)
Witzig 2004
Witzig 2004 344333proportiondied during study period13/1688/165NR
Witzig 2004 344333proportiondied within 30 days after the last dose31/16822/165NR
Information submitted by J&J for FDA/ODAC hearing344333Hazard ratiodouble-blind study phase plus 30 days31/16826/165HR 1.17 (0.69; 1.97)
Witzig 2004 344330proportionfollow up 1 year105/166103/164p=0.53HR 1.09 (0.83; 1.43) calculated with p value and events, direction questionable
Witzig 2004 344330median overall survivalfollow up 1 year10.4 months11.2 monthsp=0.53
N93-004
FDA report and information submitted by J&J for FDA/ODAC hearing224224proportion3 years100/109101/115NR
FDA report and information submitted by J&J for FDA/ODAC hearing224224median survival (K-M estimate, 95% CI in months)3 years10.5 (9; 13)10.4 (8; 13)NR
Henke 2003
Henke 2003 351351Cox model, adjusted for stratum and AJCC stage, ITTEPO: 605 days, control 928 days109/18089/171HR 1.39 (1.05–1.84)
Henke 2003 351351Cox model, adjusted for stratum and AJCC stage, radiotherapy correctEPO: 605 days, control 928 days109/18089/171HR 1.22 (0.86–1.73)
Henke 2003 351351Cox model, adjusted for stratum and AJCC stage, per protocolEPO: 605 days, control 928 days109/18089/171HR 1.13 (0.78–1.64)
Information submitted by Roche for FDA/ODAC hearing351351adjusted Cox regression, p=0.023, adjusted by stratum and TNM stagingEPO: 605 days, control 928 days109/18089/171HR 1.39 (1.05–1.84)censored: EPO 71, control 82
Information submitted by Roche for FDA/ODAC hearing351351log rank test, p=0.0901, not adjustedEPO: 605 days, control 928 days109/18089/171HR 1.27 (0.96–1.68), calculatedcensored: EPO 71, control 82
Österborg 2002
Österborg 2002 349343proportiondeaths during 16 weeks of study21/17019/173-
Österborg 2002 349343proportiondeaths during 16 weeks of study and follow up28/17022/173-
IPD data submitted by Roche
2002
349343Hazard ratiomedian observation time 113 days21/17019/173HR 1.13 (0.61; 2.09)
Information submitted by Roche for FDA/ODAC hearing349343Cox regressiondeaths until day 28 after end of treatmentNRNRHR 1.29 (0.71; 2.35)
Information submitted by Roche for FDA/ODAC hearing349343logrank test
p=0.76
median survival (months): EPO 17.4, control 18.3110/170109/173HR 1.04 (0.80; 1.36), calculated by JBcensored: EPO 60, control 64
Österborg 2005 349343min follow up 17.5 months, median time for patients being censored EPO 27.8 months. Control 27.5 months; median survival (months): EPO 17.4 (95% CI 15.0; 20.5), control 18.3 (95% CI 16.0–22.3), log-rank test: p=0.76110/170109/173HR 1.04 (0.80; 1.36), reportedcensored: EPO 60, control 64
Cazzola 1995
Cazzola 1995 146146ProportionNR4/1173/29NR
IPD data submitted by Roche 2002146146IPD based hazard ratiomedian observation time 57 days2/1171/29HR 0.06 (0.00; 3.53)
Information submitted by Roche for FDA/ODAC hearing146146Cox regressiondeaths until day 28 after end of treatmentNRNRHR 0.37 (0.06; 2.25)
Coiffier 2001; Boogaerts 2003
Boogaerts 2003 262262NRNRNRNRNR
IPD data submitted by Roche 2002262262IPD based hazard ratiomedian observation time 85 days8/1338/129HR 1.02 (0.38; 2.72)
Roche submission 2004262259Cox regressiondeaths until day 28 after end of treatmentNRNRHR 1.02 (0.42; 2.46)
Oberhoff 1998
Oberhoff 1998 218218Proportionduring controlled treatment phase8/11414/104NR
IPD data submitted by Roche 2002218218IPD based hazard ratiomedian observation time 85 days5/11412/104HR 0.38 (0.15; 0.99)
Information submitted by Roche for FDA/ODAC hearing218218Cox regressiondeaths until day 28 after end of treatmentNRNRHR 0.61 (0.24; 1.55)
Ten Bokkel 1998
Ten Bokkel 1998 122120Proportionduring study or subsequent follow up6/872/33NR
IPD data submitted by Roche 2002122120IPD based hazard ratiomedian observation time 169.5 days4/872/33HR 0.80 (0.14; 4.70)
Information submitted by Roche for FDA/ODAC hearing122116Cox regressionNRNRHR 1.01 (0.19; 5.25)
Österborg 1996 a, b
Österborg 1996 a144144Proportiondeaths during study period15/4714/49NR
Österborg 1996 bProportion11/48NR
IPD data submitted by Roche 2002 (a)144144IPD based hazard ratiomedian observation time 168.5 days15/4712/49HR 1.34 (0.55; 3.30)
IPD data submitted by Roche 2002 (b)IPD based hazard ratio10/48HR 0.78 (0.27; 2.25)
Information submitted by Roche for FDA/ODAC hearing144144Cox regressiondeaths until day 28 after end of treatmentNRNRHR 1.02 (0.51; 2.05)
Rose 1994
only unpublished data (extracted from CSR by JB)*221Proportionsimple binary approach11/1424/791.52 (0.51; 4.53)
Information submitted by J&J for FDA/ODAC hearing221Hazard ratiodouble-blind study phase plus 30 days16/1426/79HR 1.68 (0.66; 4.30)
Case 1993
unpublished data157Proportionsimple binary approach10/819/761.05 (0.40; 2.73)
Information submitted by J&J for FDA/ODAC hearing157Hazard ratiodouble-blind study phase plus 30 days10/819/76HR 1.08 (0.44; 2.67)
Dammacco 2001
published and unpublished data identical145Proportionsimple binary approach1/697/760.23 (0.05; 0.94)
Information submitted by J&J for FDA/ODAC hearing145Hazard ratiodouble-blind study phase plus 30 days1/697/76HR 0.15 (0.02; 1.20)
Henry 1995
only unpublished data132Proportionsimple binary approach8/6710/650.75 (0.28; 2.01)
Information submitted by J&J for FDA/ODAC hearing132Hazard ratiodouble-blind study phase plus 30 days8/679/65HR 0.86 (0.33; 2.22

From: Appendix C, Evidence Tables

Cover of Comparative Effectiveness of Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment
Comparative Effectiveness of Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment [Internet].
Comparative Effectiveness Reviews, No. 3.
Seidenfeld J, Piper M, Bohlius J, et al.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.