Time to Disease Progression Study M00-211

1
Time to Disease ProgressionStudy M00-211 ITT
P (G1,1) .136
HR 0.885 (95 CI 0.755 1.037)
Scheduled radiographic scans
2
Time to Disease Progression Study M00-211
Patients with Bone Metastases
P .016
HR 0.813 (95 CI 0.685 0.965)
3
Time to Disease ProgressionOBrien-Fleming
AdjustmentStudy M00-211Patients with Bone
Metastases
P .023
HR 0.818 (95 CI 0.691 0.968)
4
Summary of Endpoints
ITT
Time to disease progression HR 0.885 (0.755, 1.037) P .123


5
Summary of Endpoints
ITT
Time to disease progression HR 0.885 (0.755, 1.037) P .123
BAP P .001
PSA P .023


6
Summary of Endpoints
ITT
Time to disease progression HR 0.885 (0.755, 1.037) P .123
BAP P .001
PSA P .023
Prostate Cancer Subscore P .032
PCS pain P .015
7
Summary of Endpoints
ITT Bone metastases(Unadjusted)
Time to disease progression HR 0.885 (0.755, 1.037) P .123 HR 0.813 (0.685, 0.965) P .021
BAP P .001 P lt .001
PSA P .023 P .015
Prostate Cancer Subscore P .032 P .035
PCS pain P .015
8
Summary of Endpoints
ITT Bone metastases(Unadjusted) Bone metastases(OBrien-Fleming)
Time to disease progression HR 0.885 (0.755, 1.037) P .123 HR 0.813 (0.685, 0.965) P .021 HR 0.818(0.691, 0.968) P .023
BAP P .001 P lt .001
PSA P .023 P .015
Prostate Cancer Subscore P .032 P .035
PCS pain P .015
9
Course of StudyStudy M00-211

• Powered to detect a treatment difference at 650
  events
• June 2001 Study initiated
• Sept. 2002 IDMC halts enrollment at 809
  patients
• Jan. 2003 IDMC recommends study stop (343
  events)
• Feb. 2003 Sites notified of study closure
• Mar. 2003 Last patients final visit (610
  events)
• May 2003 Study blind broken
• Study blind maintained through collection of
  events

10
Time to Disease Progression Study M96-594 ITT
10 mg vs. placebo
P .132
HR 0.769 (95 CI 0.545, 1.085)
11
Group Sequential Stopping Rule

• One-sided symmetric (Emerson and Fleming, 1989)
• Type I error 0.025, power 90
• Conservative early boundaries
• Efficacy reject null hypothesis
• Futility reject alternative of effect similar
  to M96-594
• G1,1 statistic

12
Time to Radiographic ProgressionStudy M00-211
Patients With Bone Metastases
P .080
HR 0.846 (95 CI 0.698 1.025)
Events 212/355 (59.7) Events 206/335 (61.5)