1 / 31

Xeloda and Xeloda-based combinations in the treatment of MBC

Xeloda and Xeloda-based combinations in the treatment of MBC. Steffan Kahlert Insert affiliation. Tumour/TP-activated oral Xeloda. Intestine. Liver. Xeloda. Xeloda. Tumour >> healthy tissue. CE. 5 ' -DFCR. 5 ' -DFCR. CyD. CyD. 5 ' -DFUR. 5 ' -DFUR. Thymidine phosphorylase (TP).

gazit
Download Presentation

Xeloda and Xeloda-based combinations in the treatment of MBC

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. Xeloda and Xeloda-based combinations in the treatment of MBC Steffan Kahlert Insert affiliation

  2. Tumour/TP-activated oral Xeloda Intestine Liver Xeloda Xeloda Tumour >> healthy tissue CE 5'-DFCR 5'-DFCR CyD CyD 5'-DFUR 5'-DFUR Thymidine phosphorylase (TP) 5-FU 5'-DFCR = 5'-deoxy-5-fluorocytidine; 5'-DFUR = 5'-deoxy-5-fluorouridine; CyD = cytidine deaminase; CE = carboxylesterase

  3. Patientcharacteristics Age Preference Comorbidities e.g. diabetes, impairedcardiac function Performance status Prior adjuvantchemotherapy Diseasecharacteristics Cumulative doseof anthracyclines Sites ofmetastases Tumorburden Long-termside effects Disease-freeinterval Tumor biology Increasing useof taxanes Cardiacimpairment Patient and disease characteristics influence treatment decisions Sequenceversus combination Trial vs clinicpatients

  4. Xeloda monotherapy: highly active first-line therapy for MBC CMF = cyclophosphamide, methotrexate, 5-fluorouracil TTP = time to progression 1Talbot D et al. Br J Cancer 2002;86:1367–72 2O’Shaughnessy J et al. Ann Oncol 2001;12:1247–54

  5. Xeloda monotherapy in patients ≥65 years: highly effective in first-line MBC Bajetta E et al. J Clin Oncol 2005;23:2155–61

  6. First-line Xeloda: similar high activityto anthracyclines and taxanes in MBC 1Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8 2Reynoso N et al. Breast Cancer Res Treat 2005;94(Suppl. 1):S219 (Abst 5039) 3Paridaens R et al. J Clin Oncol 2000;18:724–33; 4Alexandre J et al. J Clin Oncol 2000;18:562–73 5Sjöström J et al. Eur J Cancer 1999;35:1194–201 ; 6Dieras V et al. Semin Oncol 1995;22(Suppl. 8):33–9 7Nabholtz J et al. J Clin Oncol 1996;14:1858–67; 8Miller KD et al. Breast Cancer Res Treat 2005;94:S6 (Abst 3)

  7. Large body of evidence with Xeloda in taxane-pretreated MBC • Five trials in 730 patients evaluated Xeloda monotherapy1 • pivotal USA (n=163) • confirmatory US/French (n=75) • German (n=136) • French (n=126) • US Xeloda ± Avastin (n=462) • Xeloda dose in all trials was 1250mg/m2 twice daily for 14 days, followed by a 7-day rest period Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8

  8. Xeloda: consistently high activity in taxane-pretreated MBC • Xeloda is more effective than other monotherapies, p=0.0052 1Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8 2Miles D et al. Clin Breast Cancer 2004;5:273–8

  9. Favorable safety of single-agent Xeloda in all patient groups

  10. Xeloda monotherapy in MBC: low incidence of grade 3/4 adverse events (n=713) Patients (%) • Minimal alopecia and myelosuppression • No cumulative toxicity • No treatment-related deaths 40 30 20 10 0 Hand-foot Diarrhoea Fatigue Stomatitis Nausea Dehydration syndrome Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8

  11. Xeloda monotherapy: minimal myelosuppression (n=498) Patients (%) 40 20 0 Grade 3 Grade 4 Leukopenia Neutropenia Anemia Thrombo- cytopenia Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8

  12. Xeloda 1000mg/m2 twice daily in patients ≥65 years Patients (%; n=43) 80 60 40 20 0 Grade 3/4 Grade 1/2 Fatigue HFS Nausea Diarrhea Stomatitis Neutropenia • Grade 3/4 diarrhea: 13% with 1250mg/m2, 2% with 1000mg/m2 • Efficacy of the two starting doses was similar (n=73) Bajetta E et al. J Clin Oncol 2005;23:2155–61

  13. Xeloda treatment improves QoL in women with MBC (n=1125) • Overall QoL stable or improved in >70% of patients Maintained Improved (p<0.01) Patients (%) 80 60 40 20 0 Function: Physical Role Emotional Social Cognitive Segalla J et al. Eur J Cancer Suppl 2005;3:115 (Abst 410)

  14. MOSG: first-line Xeloda sequence or combination? n=345 RANDOMI ZAT ION X825T75(n=71) X825P175 (n=73) T100 (n=21) X1250 (n=62) PD P175 (n=4) PD = disease progression MOSG = Mexican Oncology Study Group Reynoso N et al. Breast Cancer Res Treat 2005;94(Suppl. 1):S219 (Abst 5039)

  15. First-line Xeloda sequence compares favourably with combinations Reynoso N et al. Breast Cancer Res Treat 2005;94(Suppl. 1):S219 (Abst 5039)

  16. Sequential Xeloda and taxanes is cost-saving • Xeloda followed by a taxane is cost-saving with similar efficacy to the combinations Reynoso N et al. Breast Cancer Res Treat 2005;94(Suppl. 1):S219 (Abst 5039)

  17. Tailoring treatment to patients with single-agent Xeloda • First-line Xeloda is a highly active, well-tolerated, cost-effective option for patients • with slowly progressing disease/low risk • where QoL issues are paramount • who are older or less fit • after adjuvant anthracyclines and taxanes

  18. First-line MBC: expanding treatment options with rationally designed Xeloda combinations A standard of care treatment option for extending survival: fit patients with rapidly progressing disease and/or visceral metastases XT Xeloda XP ± Herceptin XN XT = Xeloda + Taxotere; XP = Xeloda + paclitaxel; XN = Xeloda + vinorelbine

  19. Taxotere Xeloda XT XT: preclinical synergy Tumour volume change (cm3) MX-1 breast cancer xenografts 6.0 5.0 4.0 3.0 2.0 1.0 0.0 –1.0 Control 14 18 22 26 30 34 38 42 Days p<0.05 for each arm versus XT Sawada N et al. Clin Cancer Res 1998;4:1013–9

  20. Addition of Xeloda to Taxotere extends survival Survival benefit maintained in aggressive disease XT (n=255) Taxotere (n=255) Overall population1 XT Taxotere Relapse ≤2 years2 Hazard ratio = 0.77 Log-rank p = 0.013 11.5 14.5 2Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8 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

  21. XT: superior response rate and TTP Estimated probability 1.0 0.8 0.6 0.4 0.2 0.0 Response rate XT (n=255) 42% Taxotere (n=256) 30% p=0.006 Log-rank p=0.0001 4.2 6.1 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Months O’Shaughnessy J et al. J Clin Oncol 2002;20:2812–23

  22. XT significantly more active than sequential TX in first-line MBC Beslija S et al. Eur J Cancer Suppl 2005;3:118 (Abst 407)

  23. XT (n=50) T X (n=50) Xeloda/Taxotere vs TX: survival advantage with 74% cross-over Survival probability 1.0 0.8 0.6 0.4 0.2 0.0 Hazard ratio = 0.53 p = 0.006 19 22 0 5 10 15 20 25 30 35 40 Months Beslija S et al. Eur J Cancer Suppl 2005;3:118 (Abst 407)

  24. XT (n=50) T X (n=50) Acceptable safety of XT versus Taxotere (grade 3/4) Patients (%) 40 30 20 10 0 HFS Fatigue Edema Stomatitis Alopecia Diarrhea Neutropenia Neutropenic fever Beslija S et al. Eur J Cancer Suppl 2005;3:118 (Abst 407)

  25. O’Shaughnessy trial: XT dose reduction does not compromise efficacy – OS Survival probability 1.0 0.8 0.6 0.4 0.2 0.0 Cycle 2 dose Both full, X1250T75 Both reduced, X1000T60 14.6 15.0 0 5 10 15 20 25 30 35 40 45 50 Months F. Hoffmann-La Roche, data on file

  26. Both full dose, X1250T75 (670 cycles) Both reduced dose, X1000T60(405 cycles) O’Shaughnessy trial: less grade 3/4 toxicity after XT doses reduced Cycles (%) • The Xeloda label recommends a reduced starting dose for patients with moderate renal impairment or those aged ≥60 years at baseline 20 16 12 8 4 0 Diarrhea Stomatitis Hand-foot Neutropenic syndrome fever Leonard R et al. Semin Oncol 2004;31(Suppl. 10):21–8

  27. Quality of life not compromised with XT Global health status XT Taxotere 80 70 60 50 40 0 0 6 12 18 24 30 36 42 48 Weeks O’Shaughnessy J et al. J Clin Oncol 2002;20:2812–23

  28. Xeloda/paclitaxel: consistent activity in MBC 1Batista N et al. Br J Cancer 2004;90:1740–6; 2Gradishar W et al. J Clin Oncol 2004;22:2321–7 3Blum J et al. Breast Cancer Res Treat 2004;88(Suppl. 1):S202 (Abst 5053) 4Susnjar S et al. J Clin Oncol 2005;23:90s (Abst 851); 5Uhlmann C et al. Oncology 2004;67:117–22

  29. Favorable safety profile of q3w XP: low incidence of grade 3/4 adverse events Gradishar W et al. J Clin Oncol 2004;22:2321–7 Batista N et al. Br J Cancer 2004;90:1740–6

  30. Xeloda/vinorelbine: consistently high activity in MBC 1Ghosn M et al. J Clin Oncol 2005;23:46s (Abst 673) 2Stuart N et al. Proc Am Soc Clin Oncol 2003;22:46 (Abst 183) 3Ahn J et al. Proc Am Soc Clin Oncol 2003;22:54 (Abst 216)4Welt A et al. Ann Oncol 2005;16:64–95Estevez L et al. Ann Oncol 2004;15(Suppl. 3):iii44 (Abst 166P)

  31. XT Xeloda XP ± Herceptin XN Xeloda-based regimens: expandingoptions for the first-line treatment of MBC • Xeloda is a highly effective and well-tolerated combination partner, allowing tailoring of treatment • Xeloda should be considered a first-line agent of choice in single-agent setting

More Related