Xeloda combinations: adaptation in a constantly changing environment

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Xeloda combinations adaptation ina constantly
changing environment
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Improving survival in first-line MCRC
12 13 14 15 16 17 18 19 20 21 22 23 24
Months
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Xeloda can replace 5-FU/LV as the backbone of
combination therapy

• Bolus 5-FU/LV not optimal in combination
• safety concerns with oxaliplatin or irinotecan1,2
• Infusional 5-FU/LV better in combination, but
  causes
• inconvenience and discomfort
• prolonged hospitalisation/frequent visits
• risk of central venous access complications
• Xeloda mimics infusion without these problems
• With oxaliplatin or irinotecan, Xeloda offers
  powerful, patient-oriented treatment

1Rothenberg ML et al. J Clin Oncol
20011938017 2Morton RF et al. Proc Am Soc Clin
Oncol 200120125a (Abst 495)
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Randomised trial evaluating two Xeloda
combinations in first-line MCRC

• Xeloda days 114 every 3 weeks plus
• irinotecan days 1, 8 (CAPIRI)
• oxaliplatin days 1, 8 (CAPOX)
• Similar antitumour activity (144 evaluable
  patients)
• 43 ORR with CAPIRI
• 51 with CAPOX
• Identical median progression-free (7.9 months)
  and overall survival (gt16 months)
• Favourable safety profiles with typical toxicity
  of oxaliplatin and irinotecan

Grothey A et al. Proc Am Soc Clin Oncol
200322255 (Abst 1022)
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Evolving combination treatment Xeloda plus
irinotecan (XELIRI)
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XELIRI in first-line MCRCUS phase II study
(n52)
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8
15
21
Day
Irinotecan 250mg/m2 as a 30-minute i.v. infusion
Xeloda 1,000mg/m2 twice daily
Day 1 (pm)15 (am)
Rest
Repeat cycle at day 22

• Male/female () 56/44 median age 58 years
• Primary tumour 84 colon, 12 rectum, 4 both
• 14 patients ?65 treated at 750/200

Patt YZ et al. ECCO 12 2003 (Poster 304)
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XELIRI showed high efficacy in first-line MCRC
1.0 0.8 0.6 0.4 0.2 0

• Response rate 46
• Stable disease 25

Estimated probability
TTP
7.1 (95 CI 5.011.1)
0 2 4 6 8 10 12 14 16 18 20 22
Months
Patt YZ et al. ECCO 12 2003 (Poster 304)
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XELIRI and FOLFIRI or IFL regimens appear to
have similar efficacy
1Patt YZ et al. ECCO 12 2003 (Poster 304)
2Grothey A et al. ASCO 200322255 (Abst 1022)
3Goldberg R et al. ASCO 200322252 (Abst 1009)
4Douillard JY et al. Lancet 200035510417
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XELIRI favourable safety profile compared with
FOLIRI or IFL regimens
1Patt YZ et al. ECCO 12 2003 (Poster 304)
2Grothey A et al. ASCO 200322255 (Abst 1022)
3Goldberg R et al. ASCO 200322252 (Abst 1009)
4Douillard JY et al. Lancet 200035510417
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Evolving combination treatment Xeloda plus
oxaliplatin (XELOX)
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XELOX international phase II trial in
first-line MCRC (n96)
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8
15
21
Day
Oxaliplatin130mg/m2 (2-hour infusion)
Xeloda1,000mg/m2 twice daily
Day 1 (pm)15 (am)
Rest
Repeat cycle at day 22

• Regimen recommended from phase I trial1
• Male/female () 64/36 median age 64 years2
• 28 prior (neo)adjuvant therapy

1Díaz-Rubio E et al. Ann Oncol 20021355865 2Van
Cutsem E et al. Proc Am Soc Clin Oncol
200322255 (Abst 1023)
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XELOX produces consistently high response rates
across subgroups
Response ()
80 60 40 20 0
61
60
60
56
55
55
55
54
53
50
Overall Liver Lung Yes No 80 gt80 lt60 ³60
Metastases (Neo)adjuvant KPS Age chemotherapy
Van Cutsem E et al. Proc Am Soc Clin Oncol
200322255 (Abst 1023)
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XELOX and CAPOX efficacies compare favourably
with FOLFOX4
1Van Cutsem E et al. ASCO 200322255 (Abst
1023) 2Grothey A et al. ASCO 200322255 (Abst
1022) 3Goldberg R et al. ASCO 200322252 (Abst
1009) 4de Gramont A et al. J Clin Oncol
200018293847
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XELOX and CAPOX favourable safety compared with
FOLFOX4
1Van Cutsem E et al. ASCO 200322255 (Abst
1023) 2Grothey A et al. ASCO 200322255 (Abst
1022) 3Goldberg R et al. ASCO 200322252 (Abst
1009) 4de Gramont A et al. J Clin Oncol
200018293847
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Improving survival in first-line MCRC
12 13 14 15 16 17 18 19 20 21 22 23 24
Months
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Survival of the fittest Xeloda is a powerful
combination partner
XELOX Avastin?
12 13 14 15 16 17 18 19 20 21 22 23 24
Months
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Continuing evolution large ongoing 1st-line
Xeloda combination programme
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Increasing diversityXeloda combinations in
adjuvant setting
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Treatment has evolved replace the dinosaur with
oral Xeloda now!
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X-panding treatment options for the future
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A natural selection oral Xeloda is the
combination partner of choice in CRC

• An effective, safe and convenient combination
  partner
• Xeloda is replacing 5-FU/LV as the backboneof
  CRC therapy