CassidyMetaAnalysisP-0177
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Transcript of CassidyMetaAnalysisP-0177
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7/28/2019 CassidyMetaAnalysisP-0177
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Cassidy J,1 Saltz L,2 Twelves C,3 Van Cutsem E,4 Hoff PM,5 Kang Y,6 Saini JPS,7 Gilberg F,7 Cunningham D8
1Glasgow University, Glasgow, Scotland; 2Memorial Sloan Kettering Cancer Center, New York, USA; 3University of Leeds, Leeds, United Kingdom; 4University Hospital Gasthuisberg, Leuven, Belgium; 5Centro De Oncologia/Hospital Si6Asan Medical Center, Seoul, Republic of Korea; 7F. Hoffmann-La Roche, Basel, Switzerland; 8The Royal Marsden Hospital, Sutton, United Kingdom
Efficacy of capecitabine vs. 5-FU in colorectal and gastric canceupdated meta-analysis of survival in 6 clinical trialsP-0177
BACKGROUND
G The oral fluoropyrimidine capecitabine has b een extensively evaluated vs. i.v.
5-fluorouracil/leucovorin (5-FU/LV) as monotherapy or as part of combinationtherapy in patients with metastatic colorectal cancer (MCRC) or advanced gastriccancer.
G On the advice of European health authorities, a meta-analysis of the efficacy ofcapecitabine vs.5-FU in MCRC and advanced gastric cancer was performed usingindividual patient data from 6 large multicenter,randomized,non-inferiority,phaseIII studies (Table 1).16
G The efficacy endpoint was overall survival.
META-ANALYSIS: RESULTS
G The meta-analysis included 6171 patients (3074 treated with 5-FU-based regimens
and 3097 treated with capecitabine-based regimens) with colorectal or gastriccancer.
G The stratified unadjusted analysis demonstrated a median overall survival for
capecitabine-based regimens of 23.1 months (95% CI:22.124.5) vs. 22.4 months(95% CI: 21.223.5) for 5-FU-based regimens, corresponding to a hazard ratio of0.94 (95% CI:0.891.0 0;p=0.0489).
G The multivariate Cox regression analysis confirmed the findings from the
unadjusted analysis. As expected, it showed that baseline ECOG performancestatus is a significant prognostic factor for overall survival.
META-ANALYSIS: METHODOLOGY
G Individual patient data were used from all studies.
G The efficacy endpoint was overall survival, which was evaluated from the time of
randomization until death from any cause. Living patients were censored at thetime of last follow-up.
G All analyses were performed on an intent-to-treat basis,i.e.all randomized patients
were included according to the allocated treatment.
G Overall survival was analyzed according to Kaplan-Meier estimates and stratified
by study. Hazard ratios and 95% CIs were calculated. Individual study data werepresented as Forest plots.
G A multivariate Cox proportional hazards model was applied to confirm the findings
from the unadjusted analysis.This model looked at the impact of prognostic factors(age,gender,b aseline ECOG performance score) on overall survival.
Table 1. Trials analyzed
S tud y Pa ti en t gro up R eg ime n No. o f pa ti en ts
SO146951 1st-line MCRC Capecitabine 3025 -F U/ LV ( Ma yo ) 3 03
SO147962 1st-line MCRC Capecitabine 3015 -F U/ LV ( Ma yo ) 3 01
M660013 R es ec te d s ta ge I II c ol on C ap ec it ab in e 1 0 045 -F U/ LV ( Ma yo ) 9 83
NO169664 1st- li ne M CR C X EL OX b ev ac iz um ab 1 01 7FOLFOX4 bevacizumab 1017
NO169675 2nd-line MCRC XELOX 313FOLFOX4 314
ML170326 1st-l in e a dv an ced g as tr ic c an ce r X P 1 60FP 156
Abbreviations:FOLFOX4,5-FU/LV + oxaliplatin;FP,5-FU + cisplatin;XELOX,capecitabine + oxaliplatin;XP,capecitabine + cisplatin.
Pres
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Survival probability
Study day
3074
3097
No.at risk
5-FU/LVCapecitabine
2361
2385
1642
1662
1175
1258
914
1007
729
787
641
703
505
537
253
275
52
56
5
6
0
0
5-FU/LVCapecitabine
0 3 00 6 00 9 00 1 20 0 1 50 0 1 8 00 2 10 0 2 4 00 2 70 0 3 0 00 3 30 0
Figure 1. Kaplan-Meier curve for overall survival
Table 2. Baseline patient characteristics
5 -F U/ LV- C ap ec it ab in e-
containing regimens containing regimens
Characteristic (n=3074) (n=3097)
Gender,%Male 58 58Female 42 42
Age,yearsMedian 60 60Range 1987 1886
ECOG performance status,%0 66 671 33 322