Capecitabine versus bolus 5 fu leucovorin as adjuvant therapy for colon cancer x act trial results
This presentation is the property of its rightful owner.
Sponsored Links
1 / 23

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


  • 108 Views
  • Uploaded on
  • Presentation posted in: General

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

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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


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


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.


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.


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.


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.


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.


X-ACT Treatment Arms Were Well Balanced

Source: Cassidy J. Presentation. ASCO 2005.


Other Prognostic Factors Were Balanced

Source: Twelves C. Presentation. ASCO 2005.


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

0123456

Years

Median follow-up 51 months

Source: Twelves C. Presentation. ASCO 2005.


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

0123456

Years

Source: Cassidy J. Presentation. Colorectal Cancer UpdateThink Tank Meeting 2005.


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

0123456

Years

Source: Cassidy J. Presentation. ASCO 2005.


Fewer Relapses in Liver and Lymph Nodes with Capecitabine


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


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


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

012345678

Months

Overall safety profile: Grade III to IV diarrhea, stomatitis, nausea, vomiting, alopecia, HFS, neutropenia

Source: Cassidy J. Presentation. ASCO 2005.


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 syndromevomiting

* p < 0.001

† Laboratory value


Capecitabine Dose Modification Reduces the Recurrence of Adverse Events

20

Grade II

Grade III

Grade IV

15

Number of cycles

10

5

0

Before AfterBeforeAfterBeforeAfter

Hand-foot syndrome Diarrhea Stomatitis


Improved Tolerability Profile of CapecitabineMaintained in Elderly


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

0122436486072

Months

No. at riskFull dose

Inter dose

Low dose

5325104594033322801941136112400

343323293265218174122813713500

12090777060503420103100


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

Baseline79161725

Weeks (of trial treatment)

n =

n =

889817894912

841746838865

Source: Cassidy J. Presentation. Colorectal Cancer UpdateThink Tank Meeting 2005.


Poststudy Chemotherapy after RelapseSimilar in Both Arms

*Also balanced first- versus second-line chemotherapy


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.


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


  • Login