Redefining the management of early breast cancer with Xeloda

1
Redefining the management of early breast cancer
with Xeloda

• Wolfgang Janni
• Ludwig-Maximilians-Universität MunichMunich,
  Germany

2
Xeloda/Taxotere (XT) rationale for use in early
breast cancer

• A pathological complete response (pCR) after
  three or four cycles of primary chemotherapy for
  stage II/III breast cancer improves clinical
  outcomes1
• Taxane use is increasing in (neo)adjuvant
  setting evidence increasingly suggests
  benefit13
• Xeloda is effective and well tolerated as
  single-agent therapy for metastatic breast
  cancer49
• XT extends survival and improves response rates
  compared with Taxotere alone10

1Bear HD, et al. J Clin Oncol 2003214165-74
2Smith IC, et al. J Clin Oncol 2002201456663Ro
ché H, et al. Breast Cancer Res Treat
200488(Suppl. 1)S16 (Abst 27)4Blum JL, et al.
J Clin Oncol 199917485-93 5Blum JL, et al.
Cancer 2001921759-686Reichardt P, et al. Ann
Oncol 200314122733 7Fumoleau P, et al. Eur J
Cancer 200440536-42 8OShaughnessy JA, et al.
Ann Oncol 2001121247-54 9Talbot D, et al. Br J
Cancer 2002861367-72 10OShaughnessy J, et al.
J Clin Oncol 2002202812-23
3
Estimated probability
1.0 0.8 0.6 0.4 0.2 0.0
XT Taxotere
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Months
1OShaughnessy J, et al. J Clin Oncol
200220281223
4
XT a manageable safety profile
Patients ()
50 40 30 20 10 0
Grade 3 Grade 4 Grade 3 Grade 4
XT (n251)
Taxotere (n255)
Hand-foot syndrome
Fatigue/ asthenia
Diarrhoea
Stomatitis
Nausea
Neutropenic fever
OShaughnessy J, et al. J Clin Oncol
200220281223
5
Fewer grade 3 / 4 adverse events afterTaxotere
and Xeloda doses are reduced
Cycles ()
20 16 12 8 4 0
Both full doses (670 cycles)
Diarrhoea Stomatitis Hand-foot Neutropenic syn
drome fever
F. Hoffmann-La Roche data on file
6
XT dose reduction does not compromise efficacy
overall survival
Estimated probability
1.0 0.8 0.6 0.4 0.2 0.0
Cycle 2 dose Both full (X 1 250mg/m2 T
75mg/m2) Both reduced (X 1 000mg/m2 T 60mg/m2)
15.0
14.6
0 5 10 15 20 25 30 35 40 45 50
Months
F. Hoffmann-La Roche data on file
7
Phase III trial XT versus AC as primary therapy
for early breast cancer
RANDO MIS ATION
SURGERY
Eligibility criteriaECOG PS 1 Stage II / III
BC Axillary lymph node involvement No prior
treatment
AC x 4 (60 / 600)
XT x 4 (1 000 / 75)
Primary
Adjuvant
AC x 4 (60 / 600)
XT x 4 (1 000 / 75)

• Primary objective pCR and cCR of PST

Ahn J-B, et al. Ann Oncol 200415(Suppl. 3)iii57
(Abst 215PD)
8
Interim analysis treatment arms well balanced
Lymph node status determined by PET or by
ultrasound-guided biopsy
Ahn J-B, et al. Ann Oncol 200415(Suppl.
3)iii57 (Abst 215PD)
9
XT highly effective versus AC
Ahn J-B, et al. Ann Oncol 200415(Suppl. 3)iii57
(Abst 215PD)
10
XT increases pCR versus AC inprimary tumours and
lymph nodes
Patients ()
XT (n65) AC (n60)
50 40 30 20 10 0
Tumours
Lymph nodes
Ahn J-B, et al. Ann Oncol 200415(Suppl. 3)iii57
(Abst 215PD)
11
Treatment-related clinical adverse events (all
grades)
Patients ()
100 80 60 40 20 0
HFS
Nausea
Myalgia
Alopecia
Vomiting
Anorexia
Diarrhoea
Stomatitis
Nail changes
Desquamation
Ahn J-B, et al. Ann Oncol 200415(Suppl. 3)iii57
(Abst 215PD)
12
Low incidence of grade 3/4 adverse events with
neoadjuvant XT versus AC
Patients ()
Ahn J-B et al. Ann Oncol 200415(Suppl. 3)iii57
(Abst 215PD)
13
XT compares favourably with AC in stage II/III
breast cancer

• pCR rate, after XT, of 20 (versus 7 after AC)
  consistent with best rates reported13
• Safety profiles differ according to the
  constituent agents, but overall adverse event
  rate similar1
• Recruitment ongoing final data in Q4 2005

1Ahn J-B, et al. Ann Oncol 200415(Suppl.
3)iii57 (Abst 215PD) 2Bear HD, et al. J Clin
Oncol 200321416574 3Ezzat AA, et al. Br J
Cancer 20049096874
14
Rationale for Xeloda asadjuvant chemotherapy

• Oral Xeloda has potential to improve adjuvant
  treatment
• highly active, alone and in combination
• well tolerated
• Highly active combination with Taxotere
• Xeloda / Taxotere improves overall survival in
  patients with metastatic BC4
• Xeloda / Taxotere has proven superiority over AC
  in neoadjuvant setting

1Blum JL, et al. Eur J Cancer 200137(Suppl.
6)S190 (Abst 693) 2OShaughnessy J, et al. Ann
Oncol 200112124754 3Segalla G, et al. Breast
Cancer Res Treat 2004(Abst 5051) 4OShaughnessy
J, et al. J Clin Oncol 200220281223
15
Registration study adjuvant XT
RANDO MIS ATION
T x 4 (100)
AC x 4
US Oncology n1 500 / 2 410 Eligibility
criteriaN12N0, tumour gt2cmN0, ER/PR
Primary endpoint DFS at 5 years
AC x 4
XT x 4 (825 bd/ 75)

• Patients with ER or PR tumours willreceive
  tamoxifen or anastrozole for 5 years

Xeloda dose days 114, q21d
16
XT improving outcomes in early breast cancer

• Xeloda offers consistently high activity with a
  favourable safety profile in metastatic BC
• Addition of Xeloda to Taxotere improves
  survivalin the metastatic setting
• Pre-operative XT improves pCR rate comparedwith
  AC
• Integration of Xeloda into adjuvant standard of
  care (AC?taxane) should improve long-term outcomes