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ATAC vs. Big 1-98

ATAC vs. Big 1-98. Patient Populations of ATAC vs. Big 1-98. Big 1-98 Differences in the Updates. First report (NEJM) was 25.8 months median follow up of 8010 patients called the primary core analysis

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ATAC vs. Big 1-98

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  1. ATAC vs. Big 1-98

  2. Patient Populations of ATAC vs. Big 1-98

  3. Big 1-98Differences in the Updates • First report (NEJM) was 25.8 months median follow up of 8010 patients called the primary core analysis • Second report (JCO ) is median follow up of 51 months on 4,922 patients.Only reporting on the two arms that randomized to either 5 years of tamoxifen or 5 years of letrozole

  4. The Hazard Ratios…They Are A-Changing !

  5. Disease Free Survival Changing Hazard Ratios in High Risk Patients

  6. ATAC DFS Hazard Ratios in Intent-To-Treat Patient Population • 16% of this group was ER negative or unknown(reduces ability to show benefit) • Node Positive Hazard Ratio=0.85 • Prior Chemotherapy Treated Patients Hazard Ratio=0.91 • Both of these fall within the benefit seen in DFS for all patients

  7. What Does It All Mean? • With longer follow up and more recurrences being seen, the benefits seen in the first analysis at 25.8 months are not holding up. At the 51 month mark the Hazard Ratios are moving closer to the value of 1 • Approximately half of the patients are still on study with only about 1200 patients having completed 5 years of therapy • To date only 15% of the patients have completed treatment in the Big 1-98 Trial • To date 92% of the patients have completed treatment in the ATAC Trial • CONCLUSION: You would expect more recurrences and hazard ratios to change even more by the conclusion of the BIG 1-98 trial

  8. Differences in Safety & Tolerability ATAC @ 68 Month vs. BIG 1-98 @ 51 Months

  9. Big-198 Safety Analysis Completed on 4895 Patients • Number of patients reporting at least one adverse event of any grade. Letrozole 2,292 vs 2,165 for Tamoxifen A Difference of 127pts • More patients on Letrozole reported at least one lifethreatening or fatal Adverse Event than patients on Tamoxifen. Letrozole(113 of 2,448 vs. 92 of 2,447 patients on tamoxifen) That is 4.6% vs. 3.8%

  10. Adverse Event Comparison

  11. Arimidex vs. Letrozole QOL,Dixon,JM et al SABCS 2006 • 165 patients were given Arimidex for 3 months then Letrozole for 3 months or Letrozole for 3 months then Arimidex for 3 months. • There were a total of 19 patient withdrawals • 4 patients withdrew before the trial began • 8 patients withdrew due to side effects while taking Letrozole. This included 3 who had previously tolerated Arimidex • 2 patients withdrew on Arimidex

  12. Cardiac Events • Comparing Cardiac events from NEJM vs. Cardiac events from JCO is like watching miracles happen! • Example: Compare Grade 5 Cardiac events from NEJM( # 16) vs. Grade 5’s from JCO (#11) • JCO Table 2 –Grade 3-5 cardiac events(the serious ones) are Significantly worse for Letrozole! P=0.001 (found in footnotes)

  13. Big 1-98 Grades 3-5 Cardiac Events

  14. General Definition of Grades 3-5 Cardiac Events

  15. Overall Conclusions • With longer follow up and over 1000 patients on each arm still on trial these data are very similar to what we see on ATAC at 68 months • Letrozole patients are reporting more AE’s and Serious AE’S than patients on Tamoxifen • ATAC showed fewer patients withdrew due to AE’s on Arimidex (11%)vs (14%)on Tamoxifen. p=0.0002 • Serious AE’s were less common on Arimidex ,4.7 % vs. 9.0% p=0.0001 • AE’s related to therapy were less on Arimidex 60.9% vs. 68.4%

  16. All AI’s Are Not The Same “While efficacy appears to be similar in the trials reported to date, we may be seeing early signals of differences in tolerability. These are completely different molecules and I think we would be naïve to assume that they will have the same side effect profile” Harvey Miles et.al.

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