1. 1 Incidence and Mortality of Lung Cancer in US, 2007 Life-long risk of lung cancer: 1:12 for men; 1:16 for women Life-long risk of lung cancer: 1:12 for men; 1:16 for women –Closely correlates with smoking patterns Jemal A, et al. CA Cancer J Clin. 2007;57:43. OverallMenWomen Annual incidence213,380114,76098,620 Annual mortality160,39089,51070,880 Leading cause (29%) of cancer deaths Leading cause (29%) of cancer deaths More deaths from lung cancer than from prostate, breast, and colorectal cancers combined More deaths from lung cancer than from prostate, breast, and colorectal cancers combined 5-year survival rate (all stages): 16% 5-year survival rate (all stages): 16% Although mortality has decreased slightly, mostly in men, incidence is still rising in both genders Although mortality has decreased slightly, mostly in men, incidence is still rising in both genders

2. 2 TNM Staging of NSCLC T = primary tumor; N = nodal involvement; M = distant metastasis. Mountain CF. Chest. 1997;111:1710. Stage IAT1N0M0 Stage IBT2N0M0 Stage IIAT1N1M0 Stage IIB T2 T3 N1 N0 M0

3. 3 TNM Staging of NSCLC (cont’d) T = primary tumor; N = nodal involvement; M = distant metastasis. Mountain CF. Chest. 1997;111:1710. Stage IIIA T1–3 T3 N2 N1 M0 Stage IIIB T4 Any T Any N N3 M0 Stage IVAny TAny NM1

4. 4 Lung Cancer Histology NSCLC NSCLC –80%–85% of all lung cancers 1 –NSCLC types: squamous cell, adenocarcinoma, large cell SCLC SCLC –15% of all lung cancers 2 –Incidence declining 1. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. 2. http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. 3. http://www.cancer.org/docroot/CRI/content/CRI_2_2_1x_What_Is_Non-small_Cell_Lung_Cancer.asp Squamous Cell 3 25%–30% Adenocarcinoma 3 40% Large Cell 3 10%–15% Small Cell 3 15%

5. 5 5-Year Survival with Lung Cancer in the US Actual (%) Target (%) Limited SCLC15–2525–30 Extensive SCLC<12–5 Stage IA NSCLC70–8585–95 Stage IB NSCLC60–7070–85 Stage IIA NSCLC35–4545–60 Stage IIB NSCLC25–3535–45 Stage IIIA NSCLC5–2020–30 Stage IIIB NSCLC3–710–20 Stage IV NSCLC<12–5 DeVita Jr VT, Hellman S, Rosenberg SA, eds. Cancer of the Lung. In: Cancer: Principles & Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005;chap 31.

6. 6 Limited SCLC Combination Chemotherapy and RT EP chemotherapy combined with concurrent chest RT is well studied in limited disease EP chemotherapy combined with concurrent chest RT is well studied in limited disease Little treatment-related mortality Little treatment-related mortality CAV = cyclophosphamide/doxorubicin/vincristine; EP = etoposide/cisplatin; RT = radiation therapy. 1. Takada M, et al. J Clin Oncol. 2002;20:3054. 2. Murray N, et al. J Clin Oncol. 1993;11:336. 3. Turrisi AT, et al. N Engl J Med. 1999;340:265. Coop GroupComparisonRegimen(s)5-Year Overall Survival (%) JCOG 1 Concurrent vs sequentialEP/RT > EP  RT24 vs 18 NCI-C 2 Early vs delayed concurrentCAV/EP/RT C2 > CAV/EP/RT C6 20 vs 10 CAV/EP/RT C6 20 vs 10 ECOG/RTOG 3 BID vs QD concurrentEP/BID RT (45 Gy) > EP/QD (45 Gy) RT26 vs 16 EP/QD (45 Gy) RT26 vs 16

7. 7 SCLC Standard Therapy Limited Stage EP (4 cycles) EP (4 cycles) Concurrent chest RT Concurrent chest RT PCI for CR PCI for CR Clinical trials Clinical trials Extensive Stage EP (IP) or EP/CAV (4–6 cycles) EP (IP) or EP/CAV (4–6 cycles) CNS metastases: chemotherapy or RT CNS metastases: chemotherapy or RT Bone metastases or obstructing lesions: RT Bone metastases or obstructing lesions: RT “Window of opportunity” clinical trials “Window of opportunity” clinical trials EP = etoposide/cisplatin; RT = radiation therapy; PCI = prophylactic cranial irradiation; CR = complete responder; IP = irinotecan/cisplatin; CAV = cyclophosphamide/doxorubicin/vincristine. Courtesy of Corey L. Langer, MD.

8. 8 Current Treatment Options for NSCLC Stage I (Localized Disease) Stage II (Localized Disease) Surgery Adjuvant Treatment a,b Treatment Algorithm for NSCLC Radiation Therapy (If Unsuitable for Surgery) Adapted from http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Courtesy of Corey L. Langer, MD. a.Adjuvant therapy for stage IB is controversial. b.Post hoc subgroup analyses from CALGB and NCI-C suggest that there may be a benefit to adjuvant therapy for tumors ≥4 cm

9. 9 Stage-Specific Hazard Ratios for Survival Recent Adjuvant Trials TrialIBIIIIIA IALT IALT 10.950.930.79 JBR.10 JBR.10 20.940.59N/A ANITA ANITA 31.100.710.69 CALGB CALGB 4,50.8N/AN/A JCOG (UFT) JCOG (UFT) 60.48N/AN/A LACE LACE 70.930.830.83 Negative Positive Indeterminate Not tested 1. Arriagada R, et al. N Engl J Med. 2004;350:351. 2. Winton T, et al. N Engl J Med. 2005;352:2589-2597 3. Douillard JY, et al. Lancet Oncol. 2006;7:719. 4. Strauss GM, et al. 42nd ASCO. June 2–6, 2006. Abstract 7007. 5. Strauss GM, et al. 40th ASCO, June 5–8, 2004. Abstract 7019. 6. Kato H, et al. Proc Am Soc Clin Oncol. 2003;22. Abstract 2498. 7. Pignon JP, et al. J Clin Oncol. 2006;24(suppl). Abstract 7008.

10. 10 Current Treatment Options for NSCLC (cont’d) Treatment Algorithm for NSCLC Stage IV (Metastatic) Chemotherapy +/- Targeted Therapy 2nd-Line Docetaxel b Pemetrexed c Erlotinib 3rd-Line Gefitinib d Erlotinib e 1st-Line Gemcitabine + Platinum-based Docetaxel + Platinum-based Paclitaxel + Platinum-based a Vinorelbine Vinorelbine + Platinum-based Consolidative Chemotherapy Palliative Stage III (Locally Advanced) Chemotherapy + Radiation Therapy Neoadjuvant Chemotherapy or Chemoradiation  Surgery (If Suitable) a Paclitaxel/carboplatin + bevacizumab in selected patients. b After failure of prior platinum-based chemotherapy. C After prior chemotherapy. d Indicated only for those who have already demonstrated a therapeutic benefit on gefitinib. e After failure of both platinum-based and docetaxel chemotherapies. Adapted from http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

11. 11 Positive Trials of Chemoradiation for Locally Advanced NSCLC Induction:4 (CALGB 8433 1 ; RTOG 88-08, 2 French, 3 UK 4 ) Induction:4 (CALGB 8433 1 ; RTOG 88-08, 2 French, 3 UK 4 ) Concurrent:3 (EORTC 5 ; Jeremic 6,7 ) Concurrent:3 (EORTC 5 ; Jeremic 6,7 ) Concurrent vs sequential:3 (Furuse 8 ; RTOG 9 ; Czech 10 ) Concurrent vs sequential:3 (Furuse 8 ; RTOG 9 ; Czech 10 ) Consolidation:0 (SWOG 9504 11 ; HOG 12 ; BTOG 13 ) Consolidation:0 (SWOG 9504 11 ; HOG 12 ; BTOG 13 ) Targeted treatment:0 (SWOG 0023 14 ; RTOG 0234 15 ) Targeted treatment:0 (SWOG 0023 14 ; RTOG 0234 15 ) 1. Dillman RO, et al. J Natl Cancer Inst. 1996;88:1175. 2. Sause WT, et al. J Natl Cancer Inst. 1995;87:195. 3. Le Chevalier T, et al. J Natl Cancer Inst. 1991;83:417. 4. Cullen MH, et al. J Clin Oncol. 1999;17:3188. 5. Schaake-Koning C, et al. Lung Cancer. 1994;10(suppl 1):S263. 6. Jeremic B, et al. J Clin Oncol. 1996;14:1065. 7. Jeremic B, et al. J Clin Oncol. 1995;13:452. 8. Furose K, et al. J Clin Oncol. 1999;17:2692. 9. Glisson B, et al. J Clin Oncol. 2000;18:2990. 10. Zatloukal P, et al. Lung Cancer. 2004;46:87. 11. Gandara DR, et al. J Clin Oncol. 2003;21:2004. 12. Hanna NH, et al. Abstract 7063. J Clin Oncol. 2006;24(June 20 suppl):18S. 13. Unpublished data. 14. Kelly K, et al. 41st ASCO. May 13–17. Abstract 7058. J Clin Oncol. 2005;23(June suppl):16S. 15. [please supply].

12. 12 Metastatic NSCLC Survival Advances Courtesy of Corey L. Langer, MD. 100 Best Supportive Care (BSC) Cisplatin New Therapies Survival (yr) 90 80 70 60 50 40 30 20 10 0 01 2 345 Percentage

13. 13 Randomized Trials with CT +/- Targeted Therapies in Treatment-Naive NSCLC THERAPYTARGETCTGROUPCOMMENT Gefitinib 1 EGFRGCAstraZenecaClosed, no benefit Gefitinib 2 EGFRPCAstraZenecaClosed, no benefit Erlotinib 3 EGFRPCGenentech/OSIClosed, no benefit Erlotinib 4 EGFRGCGenentech/OSIClosed, no benefit AG3340 5 MMPPCAgouronClosed, no benefit AG3340 6 MMPGCAgouronClosed, no benefit BMS275291 7 MMPPCBMSOClosed, no benefit Lonafarnib 8 FT (ras)PCScheringClosed, no benefit Isis 3521 9 PKC  PCIsisClosed, no benefit Bexarotene 10 RXRPCLigandClosed, no benefit Bevacizumab 11 VEGFPCECOGClosed, positive 1. Giaconne G, et al. J Clin Oncol. 2004;22:777. 2. Herbst RS, et al. J Clin Oncol. 2004;22:785. 3. Herbst RS, et al. J Clin Oncol. 2005;23:5892. 4. Gatzemeier U, et al. Abstract 7010. J Clin Oncol. 2004;22(July suppl): 7010. 5. Smylie M, et al. Abstract 1226. Proc Am Soc Clin Oncol. 2001;20:307a. 6. Bissett D, et al. J Clin Oncol. 2005;23:842. 7. Leighl NB, et al. J Clin Oncol. 2005;23:2831. 8. Schering-Plough press release. Available at: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/02-05- 2004/0002104279&EDATE=. Accessed April 17, 2007. 9. Lynch T, et al. J Clin Oncol. 10. Blumenschein GR, et al. Abstract 7001. J Clin Oncol. 2005;23(June 1 suppl):16S. 11. Sandler A, et al. N Engl J Med. 2006;355:2542. EGFR = epidermal growth factor receptor; GC = gemcitabine + carboplatin; FT (ras) = farnesyl transferase (Ras protein); PKC  = protein kinase C-alpha; RXR = retinoid X receptor; CT = chemotherapy; GC = gemcitabine + carboplatin; PC = paclitaxel + carboplatin.