Duffaud F et al. ASCO 2009; Abstract 10508. (Oral Presentation)

1. Time to Secondary Resistance (TSR) After Interruption of Imatinib: Updated Results of the Prospective French Sarcoma Group Randomized Phase III Trial on Long Term Survival Duffaud F et al. ASCO 2009; Abstract 10508. (Oral Presentation)

2. Introduction • 85%-90% of patients with GIST experience tumor control with imatinib (IM) • Previous studies suggest that IM therapy should be administered continuously until disease progression or intolerance and not interrupted in responding patients • The impact of IM re-introduction at disease progression on time to secondary resistance (TSR) remains unknown • Current study objectives (N = 432): • Assess the impact on PFS and TSR of interrupting first-line IM therapy after 1, 3 and 5 years in responding patients with advanced or metastatic GIST Source:Blay JY et al. J Clin Oncol 2007;25(9):1107-13.

3. BFR14 Phase III Trial Design Evaluate for Randomization at 1 yr, 3 yrs, 5 yrs StopImatinib DiseaseProgression RestartImatinib400 mg daily Advanced/metastatic GIST on imatinib R Stable Disease or better ContinueImatiniband Follow-up ContinueImatinib400 mg daily Surgery possible if resectable Source: Duffaud F et al. ASCO 2009; Abstract 10508.

4. Effect of IM Treatment Interruption on PFS 1 Rate of SRafter randomization to IM = first progression in the CONT arm and second progression in the STOP arm 2 Five year randomization group insufficient data to report Source: Duffaud F et al. ASCO 2009; Abstract 10508.

5. Rate of Secondary Resistance in Patients That Have Interrupted IM Treatment The rate of secondary resistance appearsto decrease with longer duration of imatinib treatment 1.0 0.9 0.8 0.7 0.6 1 year STOP arm: 15 evts/32 patients 2 years PFS: 63% CI95 = [43 - 78] 3 years STOP arm: 6 evts/25 patients 2 years PFS: 87% CI95 = [64 - 96] Survival probability 0.5 0.4 0.3 0.2 Log-rank p-value = 0.129 0.1 0.0 0 6 12 18 24 30 36 42 48 54 60 66 72 Months Rate of Relapse-2 Year Follow Up 1 Year Randomization Group: 40% 3 Year Randomization Group: <20% Source: With permission from Duffaud F et al. ASCO 2009; Abstract 10508.

6. Summary and Conclusions • Interruption of IM treatment in patients with GIST who have achieved stable disease or better results in rapid disease progression • 1-Year Randomization: Median TTP CONT = 31.4 mos vs STOP = 7.3 mos • 3-Year Randomization: Median TTP CONT = Not reached vs STOP = 9.4 mos • Re-introduction of IM treatment to patients in the STOP arms after a new progression allowed for tumor control • 92% of patients (23/25) in the 1 year group • 100% of patients (20/20) in the 3 year group • Interruption of IM treatment does not hasten development of secondary resistance upon re-introduction of treatment • Rate of secondary resistance appears to decrease with longer duration of IM treatment • Results with patients randomized to interrupt IM after 5 years of therapy will be available for ASCO 2010 Source: Duffaud F et al. ASCO 2009; Abstract 10508.

7. Outcome of Patients with Advanced GIST Achieving a Complete Remission (CR) with Imatinib (IM) Before Interruption: Pooled Analysis of Two Consecutive Prospective Randomizations of the French Sarcoma Group BFR14 Phase III Trial Chevreau C et al. ASCO 2009; Abstract 10549. (Poster)

8. Introduction • Optimal duration of IM treatment is unknown, but treatment interruption in responding patients after 1-3 years leads to high risk of rapid progression within a few months (See Duffaud ASCO 2009;Abstract 10508) • Current study objectives: • Determine PFS of patients in the STOP group achieving a CR or a significant PR (residual tumor < 10 millimeters by CT scan) before IM interruption compared to the outcome of patients in the STOP group who experienced other patterns of response Source: Chevreau C et al. ASCO 2009; Abstract 10549.

9. Median PFS of Patients With Interrupted IM Treatment 1 Includes patients for five-year IM treatment group (four responders, three nonresponders) * Responders = Patients who achieved CR or significant PR (residual tumor <10mm by CT scan) Source: Chevreau C et al. ASCO 2009; Abstract 10549.

10. Relapse Events in Patients With Interrupted IM Treatment 1 Includes patients for five-year IM treatment group (four responders, three nonresponders) * Responders = Patients who achieved CR or significant PR (residual tumor <10mm by CT scan) Source: Chevreau C et al. ASCO 2009; Abstract 10549.

11. Absence of Liver Involvement Correlates To Patients Achieving Response to IM Treatment Prior to Randomization † Includes one additional responder from five-year IM treatment group not included in progression analyses *Responders = Patients who achieved CR or significant PR (residual tumor <10mm by CT scan) Source: Chevreau C et al. ASCO 2009; Abstract 10549.

12. Summary and Conclusions • CR obtained under IM treatment is a prerequisite for prolonged disease-free survival in advanced GIST • 35% of all responding patients (CR or significant PR with residual tumor <10mm by CT scan) that interrupted IM treatment remained relapse-free versus only 12% of the non-responders • Longer period of IM treatment prior to treatment interruption may delay the onset of first progression • Median PFS in the responders for one-year versus three-year treatment groups (9.4mo versus 14.1mo, respectively) • Absence of liver invasion may serve as a marker for favorable response to IM treatment • Absence of liver invasion was statistically correlated (p = 0.009) with complete or significant partial response to IM in this study Source: Chevreau C et al. ASCO 2009; Abstract 10549.