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