Elderly and PS 2 Patients With Advanced NSCLC Winter Lung Cancer Conference 2012

1. Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw, unedited content. Select slides from the original presentation are omitted where Research To Practice was unable to obtain permission from the publication source and/or author. Links to view the actual reference materials have been provided for your use in place of any omitted slides.

4. Elderly and PS 2 Patients With Advanced NSCLCWinter Lung Cancer Conference2012 Rogerio Lilenbaum, MD, FACP Cleveland Clinic Florida Weston, FL

5. Elderly and PS 2 Patients With Advanced NSCLC • Combination vs. Single Agent Therapy • Bevacizumab with chemotherapy • Targeted agents in unselected patients

6. IFCT Study Schema NSCLC Stage III-IV Age 70-89 years PS 0-2 n = 451 Vinorelbine or Gemcitabine* R A N D O M Erlotinib** 150 mg/d Carboplatin + paclitaxel Stratification by center, PS 0-1 vs. 2, age ≤80 vs. >80 and stage III vs. IV *Choice of the center at the beginning of the study; ** In case of PD or excessive toxicity Ref: Quoix E, Zalcman G, Oster JP, et al; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88.

7. PFS (ITT) Quoix et al • Doublet chemotherapy • Median PFS: 6.1 months (95% CI 5.5-6.9) • 1-year PFS: 15.4% (95% CI 10.8-20.8) • Monotherapy • Median PFS: 3.0 months (95% CI 2.6-3.9) • 1-year PFS: 2.3% (95% CI 0.8-5.3) • p < 10-6

8. Overall survival (ITT) Quoix et al • Doublet chemotherapy • MST = 10.3 months (95% CI 8.3-13.3) • 1-year survival 45.1% (95% CI 38.2-51.8) • Monotherapy • MST = 6.2 months (95% CI 5.3-7.4) • 1-year survival 26.9% (95% CI 21-33.1) • p = 0.00004

9. Exploratory Sub-group analysis "Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC."

10. Brazilian PS2 NSCLC: Trial Design Pemetrexed 500 mg/m2 IV q 21 days (max 4 cycles) R A N D O M I Z E Chemotherapy-naive patients with stage IIIB (with pleural effusion) or IV NSCLC and ECOG PS 2 N= 208 Carboplatin AUC=5 IV q 21 days Pemetrexed 500 mg/m2 IV q 21 days (max 4 cycles) Primary Objective: OS Trial closed – submitted to ASCO 2012

11. Elderly and PS 2 Patients With Advanced NSCLC Combination vs. Single Agent Therapy Elderly: Yes PS 2: TBD Bevacizumab with chemotherapy Targeted agents in unselected patients

12. Elderly and PS 2 Patients With Advanced NSCLC Combination vs. Single Agent Therapy Bevacizumab with chemotherapy Targeted agents in unselected patients

13. Outcomes for Elderly Advanced NSCLC Patients Treated with Bevacizumab in Combination with Carboplatin and Paclitaxel: Analysis of ECOG 4599 Study *Median Age “Elderly”: 74 Ramalingan et al. JCO 2008

14. Toxicity on PCB Arm: Elderly vs. Non-Elderly

15. Outcomes for Elderly Patients Treated With Bevacizumab in Combination with Cisplatin and Gemcitabine: Analysis of the AVAIL Study Elderly Group ≥ 65* Younger Group < 65 *Median Age Elderly Group: 68 (36% 70 or older) Results reported in HR Leighl et al. JCO 2008

16. Elderly Patients : Toxicity Analysis of the AVAIL Study Only Gr≥3 PLT more frequent with Bev . Post Hoc analysis of ≥ 70 vs. 70 similar to age 65 cutoff

17. Bev in PS 2 Advanced NSCLC: TOPPS Pemetrexed 500 mg/m2 IV q 21 days R A N D O M I Z E Chemotherapy-naive patients with stage IIIB (with pleural effusion) or IV NSCLC and ECOG PS 2 Pemetrexed 500 mg/m2 IV q 21 days Bevacizumab 15 mg/kg IV q 21 days Carboplatin AUC=5 IV q 21 days Pemetrexed 500 mg/m2 IV q 21 days Bevacizumab 15 mg/kg IV q 21 days Primary Objective: PFS Secondary Objectives:ORR Toxicity OS

18. Elderly and PS 2 Patients With Advanced NSCLC Combination vs. Single Agent Therapy Bevacizumab with chemotherapy Age alone is not a contraindication to Bev Exercise caution with very old patients and/or those with significant co-morbidities or compromised PS Targeted agents in unselected patients

19. Elderly and PS 2 Patients With Advanced NSCLC Combination vs. Single Agent Therapy Bevacizumab with chemotherapy Targeted agents in unselected patients

20. Erlotinib or Chemotherapy in PS2 Patients Lilenbaum et al. JCO 2008

21. TOPICAL Endpoints • Inclusion criteria • Histologically/cytologically confirmed NSCLC • Measurable stage IIIB/IV disease and ≥ 18 yrs • Chemo-naive and unsuitable for chemotherapy:– ECOG PS 2–3 or– PS 0–1 with impaired renal function CC<60ml/min • Life expectancy ≥8 weeks Erlotinib*(150mg/day)to PD • Primary • Overall survival (OS) • Secondary • Progression-free survival (PFS) • Objective response rate • Quality of life (QoL) • Disease-related symptoms • Safety and tolerability • Translational • Biomarker analyses • – EGFR mutation– proteomic/genomic markers 1:1 randomization Placebo*to PD *+/- palliative XRT Lee SM et al ASCO 2010

22. Baseline characteristics *Asian = East, Southeast, South Asia; other = African-Caribbean

23. TOPICAL Trial Lee et al. ASCO 2010

24. OS: planned subgroups • Overall, erlotinib plus BSC did not improve OS • Clear effect on OS for females

25. Elderly and PS 2 Patients With Advanced NSCLC Combination vs. Single Agent Therapy Bevacizumab with chemotherapy Targeted agents in unselected patients First-line use of TKIs should be based on molecular selection Consider erlotinib in female patients with adenocarcinoma, if the alternative is no therapy

26. Saturday, February 11, 2012Hollywood, Florida Co-Chairs Rogerio C Lilenbaum, MD Mark A Socinski, MD Co-Chair and Moderator Neil Love, MD Faculty Chandra P Belani, MD John Heymach, MD, PhD Pasi A Jänne, MD, PhD Thomas J Lynch Jr, MD Heather Wakelee, MD