1. CRC-1 The Need for 3rd-Line Therapy in Non-Small Cell Lung Cancer Frances A. Shepherd, MD Scott Taylor Chair in Lung Cancer Research Princess Margaret Hospital Professor of Medicine, University of Toronto Frances A. Shepherd, MD Scott Taylor Chair in Lung Cancer Research Princess Margaret Hospital Professor of Medicine, University of Toronto

2. CRC-2 > 110,000 patients potential candidates for systemic therapy yearly Metastatic Resectabledisease Locally advanced Most Patients With NSCLC Will Require Systemic Therapy ~80% relapse Shepherd. Semin Oncol. 1999. ~50% relapse

3. CRC-3 Systemic Treatment for Advanced NSCLC Chemotherapy — 1st-Line  Modestly improves survival and symptoms  Platinum-based regimens the standard  Uncertain benefit in patients with PS 2  Toxicity an issue 1st- and 2nd-line  Modestly improves survival and symptoms  Platinum-based regimens the standard  Uncertain benefit in patients with PS 2  Toxicity an issue 1st- and 2nd-line

4. CRC-4 2nd-Line Treatment for NSCLC  Docetaxel is the only chemotherapy approved for NSCLC  Response rate is low –— only 6% to 7%  Demonstrated benefit in terms of survival and symptom control  Toxicity is an issue  Docetaxel is the only chemotherapy approved for NSCLC  Response rate is low –— only 6% to 7%  Demonstrated benefit in terms of survival and symptom control  Toxicity is an issue

5. CRC-5 3rd-Line Treatment for Advanced NSCLC  For NSCLC, no standard definition for disease refractory to both platinum and docetaxel  Clinical definition of 3rd-line: patients previously treated with a platinum and docetaxel who are not expected to benefit from additional treatment with same  Single-agent chemotherapy now used for 3rd-line  For NSCLC, no standard definition for disease refractory to both platinum and docetaxel  Clinical definition of 3rd-line: patients previously treated with a platinum and docetaxel who are not expected to benefit from additional treatment with same  Single-agent chemotherapy now used for 3rd-line

6. CRC-6 Massarelli et al. ASCO. 2002. Outcomes in NSCLC Patients From Start of 3rd- and 4th-Line Therapy Months after start of 3rd- or 4th-line therapy Survival probability 06 12 18 24 0.0 0.2 0.4 0.6 0.8 1.0 0.1 0.3 0.5 0.7 0.9 Objective response2.3% (n = 1) Median survival4.5 months 1-year survival5% N = 43

7. CRC-7 NSCLC Commonly Causes Disease-Related Symptoms  Specific symptoms –Shortness of breath –Cough –Tightness in the chest –Difficulty breathing –Poor Appetite and Weight loss –Fatigue  Type, severity, frequency depend on tumor location, disease burden, and growth rate  Specific symptoms –Shortness of breath –Cough –Tightness in the chest –Difficulty breathing –Poor Appetite and Weight loss –Fatigue  Type, severity, frequency depend on tumor location, disease burden, and growth rate

8. CRC-8 Significance of Objective Responses in 3rd-Line Therapy of NSCLC  Measure of antitumor activity  Associated with symptom improvement  Associated with better patient outcomes  Measure of antitumor activity  Associated with symptom improvement  Associated with better patient outcomes

9. CRC-9 Disease-Related Symptoms in NSCLC  When asked, 68% of patients with NSCLC who had already received platinum, stated they would choose chemotherapy compared to best supportive care if symptoms could be substantially reduced, even if survival was not prolonged Silvestri et al. 1998

10. CRC-10 Goals of 3rd-Line Therapy in NSCLC  Improve disease-related symptoms  Improve performance status  Treatment not an additional burden –Enhanced patient control –Holiday from IV therapy –Less time away from home for treatment  Improve disease-related symptoms  Improve performance status  Treatment not an additional burden –Enhanced patient control –Holiday from IV therapy –Less time away from home for treatment

11. CRC-11 3rd-Line Therapy for Non-Small Cell Lung Cancer: an Unmet Need  Increasing numbers of patients with NSCLC for 3rd-line therapy  Most of these patients have significant disease-related symptoms  No approved 3rd-line agents  Standard chemotherapies a poor solution  3rd-line therapy for NSCLC represents an unmet medical need  Increasing numbers of patients with NSCLC for 3rd-line therapy  Most of these patients have significant disease-related symptoms  No approved 3rd-line agents  Standard chemotherapies a poor solution  3rd-line therapy for NSCLC represents an unmet medical need