1 / 23

James Cassidy, MD Colorectal Cancer Update Think Tank Meeting June 24, 2005

Capecitabine versus Bolus 5-FU/Leucovorin as Adjuvant Therapy for Colon Cancer: X-ACT Trial Results. James Cassidy, MD Colorectal Cancer Update Think Tank Meeting June 24, 2005. X-ACT Trial in Adjuvant Treatment of Dukes’ C Colon Cancer. Capecitabine

chione
Download Presentation

James Cassidy, MD Colorectal Cancer Update Think Tank Meeting June 24, 2005

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. Capecitabine versus Bolus 5-FU/Leucovorin as Adjuvant Therapy for Colon Cancer: X-ACT Trial Results James Cassidy, MDColorectal Cancer Update Think Tank MeetingJune 24, 2005

  2. X-ACT Trial in Adjuvant Treatment of Dukes’ C Colon Cancer Capecitabine 1,250 mg/m2 twice daily, d1–14, q21d n = 1,004 Recruitment 1998–2001 • 1° endpoint: Disease-free survival (DFS) • 2° endpoints • Relapse-free survival (RFS) • Overall survival • Tolerability (NCIC CTC) • Pharmacoeconomics • QoL Chemo-naïve Dukes’ C, resection ≤8 weeks Bolus 5-FU/LV 5-FU 425 mg/m2 plus LV 20 mg/m2, d1–5, q28d n = 983 Source: Cassidy J. Presentation. ASCO 2005.

  3. X-ACT Powered to Establish at Least Equivalence of Capecitabine • Sample size to achieve • 80% power for at least equivalence in DFS • Noninferiority margin 1.25 for hazard ratio of capecitabine vs 5-FU/LV • Analysis in per-protocol and ITT populations • Secondary analyses • Test for superiority in DFS, RFS, OS Source: Twelves C et al. N Engl J Med 2005;352(26):2696-704.

  4. Standard Eligibility Criteria • Eligible patients • Aged 18–75 years • Histologically confirmed Dukes’ C colon cancer • Fully recovered after surgery • ECOG PS: ≤1 • Life expectancy ≥ 5 years • Excluded patients • Metastatic disease • Prior cytotoxic chemotherapy or organ allografts • Clinically significant cardiac disease • Severe renal impairment • Central nervous system disorders • Pregnant or lactating women Source: Twelves C et al. N Engl J Med 2005;352(26):2696-704.

  5. Protocol-Defined Populations and Endpoints • Populations • Intent to treat, all randomized patients • Per-protocol population excludes major protocol violations and patients with <12 weeks treatment • Time-related endpoints • Disease-free survival • Relapses or new occurrences of colon cancer and all deaths • Relapse-free survival • Relapses/new occurrences of colon cancer and deaths related to treatment or colon cancer • Overall survival Source: Twelves C et al. N Engl J Med 2005;352(26):2696-704.

  6. X-ACT Treatment Schedules Capecitabine1,250 mg/m2 twice daily Rest (days 15–21) Treatment (days 1–14) Repeat cycle x 8 (24 weeks) OR Day Bolus 5-FU/LV IV leucovorin20 mg/m2 + IV 5-FU 425 mg/m2 1 2 3 4 5 8 15 21 28 Repeat cycle x 6 (24 weeks) Source: Twelves C et al. N Engl J Med 2005;352(26):2696-704.

  7. X-ACT Treatment Arms Were Well Balanced Source: Cassidy J. Presentation. ASCO 2005.

  8. Other Prognostic Factors Were Balanced Source: Twelves C. Presentation. ASCO 2005.

  9. Strong Trend to Superior DFS (ITT) 1.0 0.8 0.6 0.4 Capecitabine (n = 1,004) 64.6% 5-FU/LV (n = 983) 61% HR = 0.87 (95% CI: 0.75–1.00)p < 0.0001 Estimated probability 0 1 2 3 4 5 6 Years Median follow-up 51 months Source: Twelves C. Presentation. ASCO 2005.

  10. Capecitabine versus Bolus 5-FU/LV: Superior Relapse-Free Survival (ITT) 1.0 0.8 0.6 0.4 Capecitabine (n = 1,004) 5-FU/LV (n = 983) HR = 0.86 (95% CI: 0.74–0.99)p = 0.0407 Estimated probability 0 1 2 3 4 5 6 Years Source: Cassidy J. Presentation. Colorectal Cancer UpdateThink Tank Meeting 2005.

  11. Capecitabine Showed Trend to Improved Overall Survival (ITT) Capecitabine (n = 1,004) 81.7% 5-FU/LV (n = 983) 78.3% 1.0 0.8 0.6 0.4 Estimated probability HR = 0.89 (95% CI: 0.74–1.07)p < 0.001 0 1 2 3 4 5 6 Years Source: Cassidy J. Presentation. ASCO 2005.

  12. Fewer Relapses in Liver and Lymph Nodes with Capecitabine

  13. X-ACT Mayo Comparable to Mayo in Other Trials (Dukes’ C, Colon Only) * Data points from KM curves Sources: 1 Haller DG et al. J Clin Oncol 2004; In Press2 André T et al. J Clin Oncol 2003;15:2896–9033 IMPACT. Lancet 1995;345(8955):939–44

  14. Treatment Exposure • Median dose intensity • Capecitabine 93% (quartiles 77-100%) • Bolus 5-FU/LV 92% (quartiles 78-100%) • Patients completing >12 weeks treatment at full dose • Capecitabine 75% • Bolus 5-FU/LV 67% • Majority of patients completed the full course of treatment • Capecitabine 84% completed all 8 cycles • Bolus 5-FU/LV 89% completed all 6 cycles

  15. Fewer Key Grade III/IV Toxicities and Later Onset with Capecitabine 1.0 0.8 0.6 0.4 0.2 0 5-FU/LV Capecitabine p < 0.001 Estimated probability of Grade III/IV adverse event 0 1 2 3 4 5 6 7 8 Months Overall safety profile: Grade III to IV diarrhea, stomatitis, nausea, vomiting, alopecia, HFS, neutropenia Source: Cassidy J. Presentation. ASCO 2005.

  16. Toxicity Treatment-related AEs 100 80 60 40 20 0 Capecitabine (n = 993) Bolus 5-FU/LV (n = 974) Patients (%) * * * * * * Diarrhea Stomatitis Hand-foot Neutropenia† Nausea/ Alopecia syndrome vomiting * p < 0.001 † Laboratory value

  17. Capecitabine Dose Modification Reduces the Recurrence of Adverse Events 20 Grade II Grade III Grade IV 15 Number of cycles 10 5 0 Before After Before After Before After Hand-foot syndrome Diarrhea Stomatitis

  18. Improved Tolerability Profile of CapecitabineMaintained in Elderly

  19. Capecitabine Efficacy Maintained with Appropriate Dose Reduction: DFS 1.0 0.8 0.6 0.4 0.2 0 Estimated probability Full dose capecitabine Inter dose capecitabine Low dose capecitabine 0 12 24 36 48 60 72 Months No. at riskFull dose Inter dose Low dose 532 510 459 403 332 280 194 113 61 12 4 0 0 343 323 293 265 218 174 122 81 37 13 5 0 0 120 90 77 70 60 50 34 20 10 3 1 0 0

  20. X-ACT: Quality of Life Maintained Over Time (QLQ C-30) 100 80 60 40 20 0 Global health status score 5-FU/LV Capecitabine Baseline 7 9 16 17 25 Weeks (of trial treatment) n = n = 889 817 894 912 841 746 838 865 Source: Cassidy J. Presentation. Colorectal Cancer UpdateThink Tank Meeting 2005.

  21. Poststudy Chemotherapy after RelapseSimilar in Both Arms *Also balanced first- versus second-line chemotherapy

  22. Replacement of 5-FU/LV with Xeloda is Net Cost Saving: Direct Payer Costs Net costs per patient versus 5-FU/LV (£) 4000 2000 0 –2000 –4000 1450 7 -57 -259 -1864 -3004 Total Drugs Administration Hospital Medications Consultations use Sources: Updated from Douillard J-Y et al. Ann Oncol 2004;15(Suppl 3):iii73; Cassidy J. Presentation. Colorectal Cancer Update Think Tank Meeting 2005.

  23. X-ACT Trial Conclusions • Disease-free survival for capecitabine at least equivalent to 5-FU/leucovorin • Capecitabine improved relapse-free survival • Capecitabine associated with significantly fewer adverse events • Capecitabine is an effective alternative to IV 5-FU/leucovorin as adjuvant therapy in patients with Stage III disease

More Related