1 / 16

Redefining the management of early breast cancer with Xeloda

Redefining the management of early breast cancer with Xeloda. Wolfgang Janni Ludwig-Maximilians-Universität Munich Munich, Germany. Xeloda/Taxotere (XT): rationale for use in early breast cancer.

james-sexton
Download Presentation

Redefining the management of early breast cancer with Xeloda

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Redefining the management of early breast cancer with Xeloda Wolfgang Janni Ludwig-Maximilians-UniversitätMunichMunich, 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 benefit1–3 • Xeloda is effective and well tolerated as single-agent therapy for metastatic breast cancer4–9 • XT extends survival and improves response rates compared with Taxotere alone10 1Bear HD, et al. J Clin Oncol 2003;21:4165−74; 2Smith IC, et al. J Clin Oncol 2002;20:1456–663Roché H, et al. Breast Cancer Res Treat 2004;88(Suppl. 1):S16 (Abst 27)4Blum JL, et al. J Clin Oncol 1999;17:485−93; 5Blum JL, et al. Cancer 2001;92:1759−686Reichardt P, et al. Ann Oncol 2003;14:1227–33; 7Fumoleau P, et al. Eur J Cancer 2004;40:536−42 8O’Shaughnessy JA, et al. Ann Oncol 2001;12:1247−54 9Talbot D, et al. Br J Cancer 2002;86:1367−72 10O’Shaughnessy J, et al. J Clin Oncol 2002;20:2812−23

  3. Addition of Xeloda to Taxotere extends survival ORR TTP 6.1 months 4.2 months 42% 30% XT (n=255) Taxotere (n=255) Hazard ratio = 0.77 Log-rank p=0.013 11.5 14.5 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 1O’Shaughnessy J, et al. J Clin Oncol 2002;20:2812–23

  4. XT: a manageable safety profile Patients (%) 50 40 30 20 10 0 Grade 3 Grade 4 Grade 3 Grade 4 XT (n=251) Taxotere (n=255) Hand-foot syndrome Fatigue/ asthenia Diarrhoea Stomatitis Nausea Neutropenic fever O’Shaughnessy J, et al. J Clin Oncol 2002;20:2812–23

  5. Both reduced (405 cycles) 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 syndrome 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 1250mg/m2 T 75mg/m2) Both reduced (X 1000mg/m2 T 60mg/m2) 14.6 15.0 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 • Primary objective: pCR and cCR of PST 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 (1000/75) Primary Adjuvant AC x 4 (60/600) XT x 4 (1000/75) Ahn J-B, et al. Ann Oncol 2004;15(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 2004;15(Suppl. 3):iii57 (Abst 215PD)

  9. XT: highly effective versus AC Ahn J-B, et al. Ann Oncol 2004;15(Suppl. 3):iii57 (Abst 215PD)

  10. XT increases pCR versus AC inprimary tumours and lymph nodes Patients (%) XT (n=65) AC (n=60) 50 40 30 20 10 0 Tumours Lymph nodes Ahn J-B, et al. Ann Oncol 2004;15(Suppl. 3):iii57 (Abst 215PD)

  11. XT (n=65) AC (n=60) Treatment-related clinical adverseevents(allgrades) Patients (%) 100 80 60 40 20 0 HFS Nausea Myalgia Alopecia Anorexia Vomiting Diarrhoea Stomatitis Nail changes Desquamation Ahn J-B, et al. Ann Oncol 2004;15(Suppl. 3):iii57 (Abst 215PD)

  12. AC (n=60) XT (n=65) Low incidence of grade 3/4 adverse events with neoadjuvant XT versus AC Patients (%) Ahn J-B et al. Ann Oncol 2004;15(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 reported1–3 • 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 2004;15(Suppl. 3):iii57 (Abst 215PD) 2Bear HD, et al. J Clin Oncol 2003;21:4165–74 3Ezzat AA,et al. Br J Cancer 2004;90:968–74

  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 2001;37(Suppl. 6):S190 (Abst 693) 2O’Shaughnessy J, et al. Ann Oncol 2001;12:1247–54 3Segalla G, et al. Breast Cancer Res Treat 2004;(Abst 5051) 4O’Shaughnessy J, et al. J Clin Oncol 2002;20:2812–23

  15. Registration study: adjuvant XT RANDO MIS ATION T x 4 (100) AC x 4 US Oncology n=1500/2410 Eligibility criteriaN1–2N0, tumour >2cmN0, 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 1–14, 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

More Related