XelodaTaxotere: a natural selection

1
Xeloda/Taxotere a natural selection
2
The patients perspective survival and QoL

• Adjuvant chemotherapy causes a temporary
  impairment in patients QoL1
• Majority of patients are willing to tolerate
  adjuvant chemotherapy even for a small to modest
  benefit2
• Patients with MBC were prepared to trade QoL to
  improve survival3

1Hürny C et al. Lancet 1996347127984 2Lindley
C et al. J Clin Oncol 19981613807 3McLachlan
SA et al. Breast Cancer Res Treat 19995421323
3
Post anthracyclines limited options and no
standard treatment
RR Median TTP Median OS n () (months) (months
)
Melphalan 64 9 1.8 7.1
Vinorelbine1 115 16 2.8 8.0
1Jones S et al. J Clin Oncol 199513256774
4
Taxotere improves overall survival versus
mitomycin C/vinblastine
1.0 0.8 0.6 0.4 0.2 0.0
ORR
Taxotere (n203) 30 MV (n189) 12
p0.0001
Estimated probability
Log-rank p0.01
8.7
11.4
0 6 12 18 24 30 36
Months
Nabholtz J-M et al. J Clin Oncol 199917141324
5
Overall survival driving the evolution of
breast cancer treatment
Mitomycin C/vinblastineNabholtz 1999
TaxotereNabholtz 1999
VinorelbineJones 1995
MelphalanJones 1995
Median survival (months)
6
XT versus Taxotere a large phase III trial
Xeloda 1,250mg/m2 twice daily, days 114
plusTaxotere 75mg/m2, day 1
(n255)
RANDOMISATION
3-weekly cycles
(n256)
Taxotere 100mg/m2, day 1

• Primary endpoint TTP

OShaughnessy J et al. J Clin Oncol
200220281223
7
XT superior response rate and TTP
1.0 0.8 0.6 0.4 0.2 0.0
ORR
XT (n255) 42 Taxotere (n256) 30
p0.006
Estimated probability
Log-rank p0.0001
4.2
6.1
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Months
OShaughnessy J et al. J Clin Oncol
200220281223
8
XT extends survival
1.0 0.8 0.6 0.4 0.2 0.0
XT (n255) Taxotere (n256)
Log-rankp0.013
Estimated probability
11.5
14.5
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Months
OShaughnessy J et al. J Clin Oncol
200220281223
9
XT has a manageable safety profile QoL is not
compromised
100 80 60 40 20 0
Clinical adverse events (all grades)
XT (n251) Taxotere (n255)
Patients ()
Fatigue/asthenia
Diarrhoea
Neutropenicfever
Nausea
Vomiting
Alopecia
Pyrexia
Myalgia
Arthralgia
Stomatitis
Hand-footsyndrome
OShaughnessy J et al. J Clin Oncol
200220(12)281223
10
Dosing flexibility allows managementof XT side
effects

• Practical patient management
• patient education to recognise symptoms and
  severity of side effects
• prompt treatment interruption and contact with
  physician or nurse
• adjustment to each individuals tolerable dose

11
Overall survival driving the evolution of
breast cancer treatment
Mitomycin C/vinblastineNabholtz 1999
TaxotereNabholtz 1999
Xeloda/TaxotereOShaughnessy 2002
OShaughnessy 2002
VinorelbineJones 1995
MelphalanJones 1995
Median survival (months)
12
How does XT measure up against sequential single
agents?
13
Xeloda best option after Taxotere
Overall survival
Single-agent Xeloda (n46) All other chemotherapy
(n120)
1.0 0.8 0.6 0.4 0.2 0.0
Log-rank p0.005
Estimated probability
12.3
21.0
0 4 8 12 16 20 24 28 32 36 40
Months
Miles D et al. Breast Cancer Res Treat
200169287 (Abst 442)
14
Does vinorelbine fail the survival test?
Vinorelbine-containing therapy (n71) All other
chemotherapy (n95)
1.0 0.8 0.6 0.4 0.2 0.0
Log-rank p0.94
Estimated probability
12.6
13.5
0 4 8 12 16 20 24 28 32 36 40
Months
Miles D et al. Breast Cancer Res Treat
200169287 (Abst 442)
15
Rationale for combination therapy

• Patients should be offered the opportunity to
  benefit from combination treatment
• in the Taxotere arm of the XT trial, 35 of
  patients did not receive subsequent chemotherapy
  after disease progression

Miles D et al. Breast Cancer Res Treat
200169287 (Abst 442)
16
MOSG study evaluating Xeloda and taxoids in
combination and sequence
XT Xeloda 825mg/m2 docetaxel 75mg/m2 (n60)
RANDOMI SAT ION
XP Xeloda 825mg/m2 paclitaxel 175mg/m2 (n67)
Reyes S et al. ECCO12 2003 (Abst 447)
Choice of taxoid at investigators discretion
17
Similar progression-free and overall survival in
all treatment arms
Time to PD on Xeloda if no further treatment
given or PD on sequential taxoid treatment
Reyes S et al. ECCO12 2003 (Abst 447)
18
Increasing diversity further evolution with
oral Xeloda
19
Further evolution into the adjuvant setting
20
XT passes the survival test in anthracycline-pretr
eated MBC

• XT is the only cytotoxic combination to improve
  survival beyond Taxotere1
• When combination treatment is inappropriate
• Xeloda monotherapy is convenient and highly
  effective in first line2,3
• Ongoing studies are extending XT into the
  (neo)adjuvant setting

1OShaughnessy J et al. J Clin Oncol
200220(12)281223 2Talbot D et al. Br J Cancer
200286136772 3Reyes S et al. ECCO12 2003 (Abst
447)