1. Clinical Update and Advances in the Treatment of NSCLC

3. Lung Cancer Incidence and Epidemiology

4. Leading Causes of Cancer-related Deaths 564,830 cancer deaths; 162,460 (29%) due to lung cancer 174,470 new cases of lung cancer MEN Lung and bronchus 31% † Colon and rectum 10% Prostate 9% Pancreas 6% Leukemia 4% WOMEN Lung and bronchus 26% † Breast 15% Colon and rectum 10% Pancreas 6% Ovary 6% Leading Sites* by Sex, United States, 2006 Estimates *Excludes basal and squamous cell skin cancer and carcinoma in situ, except urinary bladder. † Includes both non-small cell lung cancer (NSCLC) and small cell lung cancer. American Cancer Society. Cancer Facts and Figures, 2006 .

5. Lung Cancer: High Incidence, High Mortality American Cancer Society. Cancer Facts and Figures, 2006 .

7. Lung Cancer Subtypes Non-small Cell Lung Cancer ~85% http://www.ncbi.nlm.nih.gov. Small Cell Lung Cancer ~15% Large Cell Carcinoma 10%-15% Adenocarcinoma 35%-40% Squamous Cell Carcinoma 25%-30%

11. Non-small Cell Lung Cancer Stages: TNM Staging System Stage IV=M1 T, primary tumor; N, regional lymph nodes; M, distant metastasis. N3 N2 N1 N0 Nodes IIIB IIIA IIA IA T1 T4 T3 T2 IIIB IIIB IIIB IIIB IIIA IIIA IIIB IIIA IIB IIIB IIB IB Tumor

12. NSCLC Stages at Presentation 31% Stage III 38% Stage IV 24% Stage I 7% Stage II Mountain CF. Semin Surg Oncol. 2000;18:106-115.

13. NSCLC Survival Mountain CF. Semin Surg Oncol. 2000;18:106-115; Fry WA, et al. Cancer. 1996;77:1949-1995. Stage IV Stage IIIB Stage IIIA Stage IIB Stage IIA Stage IB Stage IA Stage Any T, Any N, M1 T4N0-3M0 T1-4N3M0 T1-2N2M0 T3N1-2M0 T2N1M0 T3N0M0 T1N1M0 T2N0M0 T1N0M0 Pathologic TNM 23% 23%-25% 39% 38% 67% <1% 5% 5% 55% 57% 5-y Survival

16. NSCLC: Stage IIIA N1: Ipsilateral peribronchial and/or hilar nodes involved N2: Ipsilateral mediastinal and/or subcarinal nodes involved M0: No distant metastasis <2 cm  2 cm T3N1-2M0 Tumor that invades chest wall, diaphragm, mediastinal pleura, parietal pericardium T1-2N2M0 T >3 cm Tumor invades visceral pleura Tumor with distal atelectasis T  3 cm; no lobar-bronchus involvement

17. Current Treatment Approaches *Strauss GM, et al. ASCO 2006. Abstract 7007. **Single-agent chemotherapy recommended for the elderly and individuals with poor performance status (PS 2). Surgical resection/adjuvant chemotherapy Stage IIB Stage IV Stage IIIB Stage IIIA Stage IIA Stage IB Stage IA Stage Surgical resection +/- adjuvant chemotherapy* Surgical resection Doublet chemotherapy** Concurrent chemotherapy/RT Surgical resection/adjuvant chemo and/or RT Concurrent chemotherapy/RT Surgical resection/adjuvant chemotherapy Standard Treatment

18. Adjuvant Therapy for Resectable Non-small Cell Lung Cancer

20. Adjuvant Therapy for Resectable NSCLC: Recommendations *Strauss GM, et al. ASCO 2006. Abstract 7007. Surgical resection +/- cisplatin-based* chemotherapy Stage IB Surgical resection in select patients + cisplatin-based chemotherapy Stage IIIA Surgical resection + cisplatin-based chemotherapy Stage II Surgical resection + observation Stage IA Recommended Treatment Stage

22. Meta-analysis of Prior Adjuvant Chemotherapy Studies Efficacy of Adjuvant Chemotherapy vs Observation Alone Non-small Cell Lung Cancer Collaborative Group. BMJ. 1995;311:899-909. 5% Absolute Benefit at 5 Years 0.08 0.87 (0.74-1.02) Meta-analysis of cisplatin-based drugs P -value Hazard Ratio (95% CI) Overall Survival by Therapy Type

23. Meta-analysis of Prior Adjuvant Chemotherapy Studies (cont.) No. at risk: Surgery plus chemotherapy 706 649 590 526 462 419 371 330 295 255 206 Surgery 688 633 648 482 433 382 353 307 258 215 177 Surgery plus chemotherapy Surgery Non-small Cell Lung Cancer Collaborative Group. BMJ. 1995;311:899-909. HR=0.86 [0.74-1.02] P =0.08 0 10 20 30 40 50 60 70 80 90 100 0 6 12 18 24 30 36 42 48 54 60 Time from randomization (months) Percentage survival

26. IALT: Patient Characteristics Le Chevalier T, et al . N Engl J Med . 2004;350:351-360. 80%/20% 81%/19% Sex (M/F) 53% 40% 7% 54% 38% 8% PS 0 1 2 59 59 Median age 935 932 N Control Chemotherapy Outcome

30. JBR.10: Effects of Vinorelbine and Cisplatin Adjuvant Chemotherapy Efficacy of Adjuvant Chemotherapy vs Observation Alone Winton T, et al. N Engl J Med . 2005;352:2589-2597. 0.03 54% 69% 5-year survival 0.009 73 months 94 months Median overall survival P -value Observation Group Chemotherapy Group Outcome

31. JBR.10: Effects of Vinorelbine and Cisplatin Adjuvant Chemotherapy P =0.006 Winton T, et al. N Engl J Med . 2005;352:2589-2597. Overall Survival, All Patients 0 20 40 100 0 2 4 6 8 10 Years Probability (%) Vinorelbine plus cisplatin Observation 60 80 Hazard ratio for death: 0.69 ( P =0.04) 69% 54%

32. JBR.10: Survival for Stage IB and Stage II Subsets No. at risk: Observation 108 91 57 29 8 0 Vinorelbine 111 91 65 27 6 0 plus cisplatin Winton T, et al. N Engl J Med . 2005;352:2589-2597. 0 20 40 60 80 100 0 2 4 6 8 10 Observation Vinorelbine plus cisplatin 0 20 40 60 80 100 0 2 4 6 8 10 Observation Vinorelbine plus cisplatin Years Probability (%) Overall Survival, Patients with Stage IB Non-small Cell Lung Cancer Overall Survival, Patients with Stage II Non-small Cell Lung Cancer No. at risk: Observation 112 91 57 18 5 0 Vinorelbine 111 100 54 24 6 0 plus cisplatin P =0.79 P =0.004 Years Probability (%)

33. JBR.10: Adjuvant Chemotherapy in the Elderly Pepe C, et al. ASCO 2006. Abstract 7009. All randomized patients N=482 Observation N=240 *18 patients who received vinorelbine 30 mg/m 2 /week excluded Prognostic factors Dose intensity (N=150 vs 63 Chemotherapy toxicities (N=150 vs 63) Elderly (>65) N=67 Young (<65) N=157 *Chemotherapy N=224

34. JBR.10: Adjuvant Chemotherapy in the Elderly Pepe C, et al. ASCO 2006. Abstract 7009. 0 2 4 6 8 10 12 1.0 0.8 0.6 0.4 0.2 0.0 H-R=0.61 Log-rank, P =0.04 Overall Survival by Treatment Arm, Age >65 Observation N=78 Chemotherapy N=77 66% 46% Time in years 0 2 4 6 8 10 12 1.0 0.8 0.6 0.4 0.2 0.0 H-R=0.66 Log-rank, P =0.13 Disease Specific Survival by Treatment Arm, Age >65 Observation N=78 Chemotherapy N=77 73% 46% Time in years Probability Probability

37. CALGB 9633: Overall Survival - ASCO 2004 vs ASCO 2006 Strauss GM, et al. J Clin Oncol. 2004;22:7019; Strauss GM, et al. ASCO 2006. Abstract 7007. ASCO: 2004 ASCO: 2006 0 2 4 6 8 Survival Time (Years) 0.0 0.2 0.4 0.6 0.8 1.0 Probability Observation Chemo 0 1 2 3 4 5 6 7 8 9 0 2 4 6 8 Survival Time (Years) 0.0 0.2 0.4 0.6 0.8 1.0 Probability Observation Chemo 0 1 2 3 4 5 6 7 8 9 HR=0.62; 90% CI: 0.44-0.89 P =0.01 HR=0.80; 90% CI: 0.60-1.07 P =0.10 Observation Chemo Observation Chemo Survival time (years) Survival time (years)

38. CALGB 9633: Disease-free Survival – ASCO 2004 vs ASCO 2006 ASCO: 2004 ASCO: 2006 0 2 4 6 8 Survival time (years) 0.0 0.2 0.4 0.6 0.8 1.0 Probability 0 1 2 3 4 5 6 7 8 9 Observation Chemo 0 2 4 6 8 Survival time (years) 0.0 0.2 0.4 0.6 0.8 1.0 Probability Observation Chemo 0 1 2 3 4 5 6 7 8 9 HR=0.69; 90% CI: 0.51-0.92 P =0.02 HR=0.74; 90% CI: 0.57-0.96 P =0.03 Strauss GM, et al. J Clin Oncol. 2004;22:7019;Strauss GM, et al. ASCO 2006. Abstract 7007.

41. ANITA: Effects of Vinorelbine and Cisplatin Adjuvant Chemotherapy Efficacy of Adjuvant Chemotherapy vs Observation Alone Douillard J, et al. ASCO 2005. Abstract 7013 . 0.013 P -value 7-year survival Median overall survival Outcome Hazard Ratio (95% CI) Observation Group Chemotherapy Group 0.79 (0.66-0.95) 36.8% 45.2% 43.8 months 65.8 months

42. ANITA: Effects of Vinorelbine and Cisplatin in Stage I (p T2N0) Disease Stage I (p T2N0) Douillard J, et al. ASCO 2005. Abstract 7013 . 0.00 0.25 0.50 0.75 1.00 0 20 40 60 80 100 OBS NVB + CDDP Months Survival distribution function Overall Survival 120 Not reached 99.7 Median months 58 61 Death NVB + CDDP n=146 OBS n=155 Stage I (p T2N0)

43. ANITA: Effects of Vinorelbine and Cisplatin in Stage II Disease Stage II Douillard J, et al. ASCO 2005. Abstract 7013 . 0.00 0.25 0.50 0.75 1.00 0 20 40 60 80 100 OBS NVB + CDDP Months Survival distribution function 120 65.8 36.5 Median months 46 70 Death NVB + CDDP n=89 OBS n=114 Stage II

44. ANITA: Effects of Vinorelbine and Cisplatin in Stage IIIA Disease Stage IIIA Douillard J, et al. ASCO 2005. Abstract 7013 . 0.00 0.25 0.50 0.75 1.00 0 20 40 60 80 100 OBS NVB + CDDP Months Survival distribution function 120 38.6 24.1 Median months 99 118 Death NVB + CDDP n=166 OBS n=159 Stage IIIA

48. LACE: Overall Survival By Trial Trials (associated drug(s)): ALPI, MTC+VDS; ANITA, NVB; BLT, NVB/VDS/MTC+VDS/MTC+IFM; JBR10, NVB; IALT, NVB/VDS/VLB/VP16. Pignon JP , et al. ASCO 2006. Abstract 7008 . OS by Trail Tests for heterogeneity: P =0.34 Chemotherapy effect: P =0.004 Chemotherapy better Control better 0.0 0.5 1.0 1.5 2.0 0.89 [0.82; 0.96] 2356/4584 Total 0.71 [0.54; 0.94] 197/482 JBR10 0.91 [0.80; 1.03] 980/1867 IALT 1.00 [0.72; 1.38] 152/307 BLT 0.82 [0.68; 0.98] 458/840 ANITA 0.95 [0.81; 1.12] 569/1088 ALPI HR [95% CI] Hazard Ratio (Chemotherapy/Control) No. Deaths/ No. Entered Trail

49. LACE: Benefit Appears to Be Stage Dependent Pignon JP , et al. ASCO 2006. Abstract 7008 . CT Effect and Stage Tests for trend: P =0.051 CT may be detrimental for stage IA, but stage IA patients were generally not given the potentially best combination cisplatin+vinorelbine (13% of stage IA patients vs ~43% for other stages) Chemotherapy better Control better 0.5 1.0 1.5 2.0 2.5 0.83 [0.73; 0.95] 865/1247 Stage III 0.83 [0.73; 0.95] 880/1616 Stage II 0.92 [0.78; 1.10] 509/1371 Stage IB 1.41 [0.96; 2.09] 102/347 Stage IA HR [95% CI] Hazard Ratio (Chemotherapy/Control) No. Deaths/ No. Entered Category

53. Management of Treatment-related Toxicities

61. 2005 NCCN Guidelines: D ecision Tree for Primary Prophylaxis Disease Intermediate10%-20% Risk 1. Evaluate 2. Assess Risk* 3. Intervene Chemotherapy Regimen Patient Risk Factors Treatment Intent High >20% Risk Low <10% Risk *Risk of FN or neutropenic event compromising treatment. Consider G-CSF Use G-CSF No Routine G-CSF

62. Clinical Benefit of Pegfilgrastim in First and Subsequent Cycles S CR E E N I NG C H EMO T H E RA P Y * RANDOM I Z A T I ON Febrile Neutropenia Placebo n = 465 Pegfilgrastim n = 463 Double-blind Phase Docetaxel + Pegfilgrastim OR Docetaxel Alone Open-label Phase * Docetaxel 100 mg/m 2 IV given on day 1 and blinded product given on day 2. Four 21- day cycles were planned. Vogel C, et al. J Clin Oncol. 2005;23:1178-1184.

63. Clinical Benefit of Pegfilgrastim in First and Subsequent Cycles (cont.) Efficacy of Pegfilgrastim for Preventing Febrile Neutropenia Vogel C, et al. J Clin Oncol. 2005;23:1178-1184. 10% 14% 17% Placebo (n=465) 80 93 94 % Reduction <0.001 2% Use of IV anti-infectives <0.001 1% Hospitalization for febrile neutropenia <0.001 1% Febrile neutropenia P -value Pegfilgrastim (n=463) Outcome

65. Prevention of FN: Growth Factor Support Misset JL, et al. Ann Oncol. 1999;10:553-560; Green MD, et al. Ann Oncol. 2003;14:29-35; Holmes FA, et al. J Clin Oncol . 2002;20:727-731. 18 20 38 9 13 0 5 10 15 20 25 30 35 40 FN rate (%) (n=42) (n=80) (n=77) (n=156) (n=154) Misset et al. Green et al. Holmes et al*. N=42 N=157 N=310 Pegfilgrastim Control Filgrastim

72. Patient-reported Areas Negatively Affected by Fatigue Vogelzang NJ, et al. Semin Hematol . 1997;34(suppl 2):4-12. 0 10 20 30 40 50 60 70 Concerns about mortality and survival Relationships with family and friends Ability to take care of family Intimacy with partner Emotional well-being Ability to enjoy life in the moment Physical well-being Ability to work Patients (%) 61 60 57 51 44 42 38 33

73. Anemia and Risk of Death 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Lung Head and neck Prostate Lymphoma Overall Relative risk of death (%) Stasi R, et al. Oncologist . 2005;10:539-554.

78. Erythropoietic Intervention Late Intervention/ Hb Correction Early Intervention/ Hb Maintenance 11 10 Erythropoietic Treatment Transfusion? Chemotherapy treatment 6 Hemoglobin (g/dL) Adapted from Rearden, TP. J Clin Oncol , 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 8064. Transfusion Chemotherapy treatment Hemoglobin (g/dL) 12 11 13 10 6 8.5 Erythropoietic Treatment 12 13 8.5

79. Clinical Benefit of Darbepoetin alfa and Epoetin alfa Schwartzberg LS, et al. Oncologist . 2004;9:696-707. Darbepoetin alfa 200  g q2 wk END OF TREATMENT 2 weeks after last dose of darbepoetin alfa or 1 week after last dose of epoetin alfa Epoetin alfa 40,000 U q wk END OF STUDY 2 weeks after end-of-treatment visit Concurrent chemotherapy 1 5 9 13 17 19 (Baseline) Study week RANDOMIZE

80. Clinical Benefit of Darbepoetin alfa and Epoetin alfa Schwartzberg LS, et al. Oncologist . 2004;9:696-707. Individual Analysis by Tumor Type 6% 27% 21% 16% 18% 17% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% Breast Lung Gyn Proportion of patients requiring a transfusion Q2W Darbepoetin alfa QW Epoetin alfa n= 72 69 51 51 34 35 Combined Analysis by Baseline Hemoglobin and Overall 21% 14% 16% 42% 9% 17% 0% 10% 20% 30% 40% 50% 60% 70% <10 g/dL > 10 g/dL Overall Proportion of patients requiring a transfusion n= 38 38 119 117 157 155 Q2W Darbepoetin alfa QW Epoetin alfa

81. Clinical Benefit of Darbepoetin alfa and Epoetin alfa Darbepoetin alfa vs Epoetin alfa for Treating Anemia Schwartzberg LS, et al. Oncologist . 2004;9:696-707. 12.2 g/dL 12.1 g/dL Mean hemoglobin level after achieving target 10.1 weeks 9.3 weeks Mean duration of treatment 4 weeks 5 weeks Median time to target hemoglobin 86% 82% Patients achieving target hemoglobin ≥11 g/dL Epoetin alfa (n=155) Darbepoetin alfa (n=157) Outcome

83. Incidence of RBC Transfusions and Sensitivity Analyses A: Percentages of patients receiving ≥ one transfusion B: Sensitivity analyses—adjusted by screening hemoglobin category (<10 g/dL vs 10 g/dL) and type of chemotherapy administered (platinum-based vs nonplatinum-based) Glaspy J, et al. J Clin Oncol . 2006;24:2290-2297. Mean (95% CI) Difference between Treatment Groups In favor of darbepoetin alfa In favor of epoetin alfa Per protocol analysis set (16 week cohort) Primary transfusion analysis set/ primary analysis set (16 week cohort) Per protocol analysis set (all cohorts) -16 -12 -8 -4 0 4 8 12 16 Noninferiority margin 11.5% 1.3% 5.0% 3.6% In favor of darbepoetin alfa In favor of epoetin alfa -16 -12 -8 -4 0 4 8 12 16 11.5% 0.4% 3.0% 4.4% 0 0.1 0.2 0.3 0.4 0.5 0.6 Darbepoetin alfa Epoetin alfa Historical (placebo) Historical (epoetin alfa) Proportion of patients (95% CI) 0 0.1 0.2 0.3 0.4 0.5 0.6 Darbepoetin alfa Epoetin alfa Historical (placebo) Historical (epoetin alfa) Proportion of patients (95% CI) 21% 16% 45% 26% 27% 22% 51% 25%

84. Effect of Darbepoetin alfa and Epoetin alfa on Hemoglobin Glaspy J, et al. J Clin Oncol . 2006;24:2290-2297. Hemoglobin (Hb) Concentration over Treatment Period Achievement of Target Hemoglobin Range (11 g/dL to 13 g/dL) by Study Week 10.18 11.44 11.75 10.21 11.76 11.85 8 9 10 11 12 13 14 Baseline Week 9 Week 17 Mean (upper 95% CI) Hb levels (g/dL) Darbepoetin alfa Epoetin alfa Target range n=606 n=603 n=433 n=431 n=278 n=245 0 0.2 0.4 0.6 0.8 1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Time (weeks) Proportion of patients Darbepoetin alfa Epoetin alfa Patients at risk: Darbepoetin alfa 606 606 586 521 395 360 290 266 220 194 164 150 122 116 98 86 69 42 Epoetin alfa 603 603 577 515 344 302 220 195 147 132 106 97 66 57 48 38 30 21

90. Neoadjuvant Therapy

94. SWOG 9900: Induction Chemotherapy Pisters K, et al. ASCO 2005. Abstract 7012. HR=0.84 [0.60-1.18] P= 0.32 0% 20% 40% 60% 80% 100% 0 12 24 36 48 60 Months Preop Control 64% 79% 40 mo Control 68% 82% 47 mo Preop 2 y 1 y Median

98. Treatment of Advanced Non-small Cell Lung Cancer

100. Best Supportive Care vs Chemotherapy in Advanced Patients Socinski M. Chest . 2003;123:226S-243S. 0 10 20 30 40 50 60 70 80 90 100 0 6 12 18 24 Time from randomization (months) Percentage survival Best supportive care (BSC) + chemotherapy Supportive care No. at risk: BSC + chemotherapy 416 219 98 47 28 Supportive care 362 125 55 28 14

101. Best Supportive Care and Chemotherapy Prolong Survival Socinski M. Chest . 2003;123:226S-243S. 0 10 20 30 40 BSC CT+BSC BSC CT+BSC 1-y survival % 5 10 15 20 No. of patients alive in the US at 1 year

104. ECOG E1594: Comparable Efficacy in Platinum-based Regimens Cis/Paclitaxel Cis/Gemcitabine Cis/Docetaxel Carbo/Paclitaxel 0 0.2 0.4 0.6 0.8 1.0 0 5 10 15 20 25 30 Months Schiller JH, et al. N Engl J Med. 2002;346:92-98. Survival by Treatment Group

105. ECOG 1594: Regimens and Efficacy Schiller JH, et al. N Engl J Med. 2002;346:92-98. 3.5 31% 7.8 21% Paclitaxel 175 mg/m 2 Cisplatin 75 mg/m 2 3.6 31% 7.4 17% Docetaxel 75 mg/m 2 Cisplatin 75 mg/m 2 4.5 36% 8.1 21% Gemcitabine 1000 mg/m 2 d1, 8, 15 Cisplatin 100 mg/m 2 d1 3.3 Time to Progression (months) 38% 1-year Survival 8.2 15% Paclitaxel 225 mg/m 2 Carboplatin AUC=6 Median Survival (weeks) Response Rate Regimen

108. Comparison of Advanced NSCLC Therapies Wakelee H, Belani CP . Oncologist . 2005;10(suppl 3):1-10. 30% 20% 10% 1 year ~10 months 6 months 4 months Median survival time Modern Doublet Chemotherapy Platinum-based Chemotherapy Supportive Care Survival <5% 10% 0% 2 years

110. Stage IV Disease: Second-line Therapy Second-line Treatment for Advanced NSCLC 1. Hanna N, et al. J Clin Oncol . 2004;22:1589-1597; 2. Shepherd FA, et al. N Engl J Med . 2005;353:123-132; 3. Shepherd FA, et al. J Clin Oncol . 2000;18:2095-2103. 7.9 months 8.8% Docetaxel NS 8.3 months 9.1% Pemetrexed Hanna et al. 1 4.6 months Best supportive care 0.047 7.0 months Docetaxel Shepherd et al. 3 4.7 months <1.0% Placebo <0.001 6.7 months 8.9% Erlotinib Shepherd et al. 2 P- value Median Survival Time Overall Response Rate Treatment Study

112. Chemotherapy Still Shows Benefits vs BSC as Second-line Therapy Shepherd FA, et al. J Clin Oncol . 2000;18:2095-2103 . 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 3 6 9 12 15 18 21 Survival time (months) Cumulative probability 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 3 6 9 12 15 18 21 Survival time (months) Cumulative probability Docetaxel 100 mg/m 2 (n=49) BSC100 (n=51) Log-rank test, P =0.780 Log-rank test, P =0.010 Docetaxel 75 mg/m 2 (n=55) BSC75 (n=49)

113. Chemotherapy Still Shows Benefits vs BSC as Second-line Therapy (cont.) Shepherd FA, et al. J Clin Oncol . 2000;18:2095-2103 . 19% 29% 1-year survival 0.047 4.6 months 7.0 months Median overall survival P -value Best Supportive Care Arms Outcome

114. Hematologic Toxicities Associated with Treatment *Incidence of grade 3/4 toxicity per patient. Shepherd FA, et al. J Clin Oncol . 2000;18:2095-2103 . 6.1 3 0 0 2.9 3 Septic deaths 22.4 11 1.8 1 11.5 12 Febrile neutropenia 2.0 1 0 0 1.0 1 Thrombocytopenia 85.7 42 67.3 37 76.0 79 Neutropenia 16.3 8 5.5 3 10.6 11 Anemia 49 55 104 Total no. of patients % No. % No. % No. 100 mg/m 2 75 mg/m 2 Overall Docetaxel * Toxicity

116. Phase III Pemetrexed vs Docetaxel for Second-line: Survival Hanna N, et al. J Clin Oncol . 2004;22:1589-1597. 0 0.25 0.5 0.75 1 0 5 10 15 20 Survival time (months) Survival distribution function Pemetrexed (n=265) Docetaxel (n=276) Patients at risk: Pemetrexed 283 189 78 16 0 Docetaxel 288 177 78 19 1 HR=0.99 (95% CI, 0.8 to 1.2) 29.7% 29.7% 1-y OS 47 mo 40 mo MST

118. Treatment in the Elderly Population and Poor Performance Status Patients

120. CALGB 9730: Monotherapy vs Combination Therapy Lilenbaum RC, et al. J Clin Oncol . 2005;23:190-196. <0.0001 30 17 Response rate, % 1-year survival, % Median failure-free survival, mo Outcome NS 27 32 0.0002 4.6 2.5 P -value Paclitaxel + Carboplatin Paclitaxel

121. CALGB 9730: Age >70 Lilenbaum RC, et al. J Clin Oncol . 2005;23:190-196. 31% 35% 1-year survival 5.8 8.0 Median survival 21% 36% Response rate Paclitaxel Paclitaxel + Carboplatin

122. CALGB 9730: PS 2 Lilenbaum RC, et al. J Clin Oncol . 2005;23:190-196. 50 40 n 14% 17% 1-year survival 2.4 4.7 Median survival 10% 24% Response rate Paclitaxel Paclitaxel + Carboplatin

124. SWOG 9308 and 9509: Retrospective Analysis in Advanced NSCLC SWOG 9308: Vinorelbine + cisplatin vs cisplatin. SWOG 9509: Paclitaxel + carboplatin vs vinorelbine + cisplatin. Kelly K, et al. ASCO 2001. Abstract 1313. 117 (19%) 79 (19%) 38 (18%) Age > 70 491 (71%) 327 (81%) 164 (82%) Age <70 Total (N=608) Vinorelbine/Cis* (N=406) Paclitaxel/Carbo (N=202) SWOG 9308 SWOG 9509

125. SWOG 9308 and 9509: Results Kelly K, et al. ASCO 2001. Abstract 1313. 22% 10% 16% 2-y OS 21% 30% 40% 1-y OS 0.06 6.9 8.6 Median survival (mo) 0.62 3.9 4.2 TTP (mo) P -value  70 (n=117) <70 (n=491)

127. ECOG 1594: Outcome Based on Age <70 y  70 y n=912 n=227 P - value Grade  4 toxicity 66% 71.2% 0.04 OR(%) 22.1 24.5 0.76 PFS (mo) PS 0-1 3.71 3.75 PFS 1-y (%) 6.5 8.6 0.37 PFS 2-y (%) 0.5 2.2 0.04 MS (mo) 8.15 8.25 1-y OS(%) 32.8 35.2 0.53 2-y OS(%) 10.6 13.7 0.24 Langer CJ, et al. ASCO 2003. Abstract 2571.

129. Efficacy of Nonplatinum Single-agent vs Doublet Chemotherapy MILES Comparison of Single-agent vs Double-agent Chemotherapy Gridelli C, et al. J Natl Cancer Inst . 2003;95:362-372. 22% 18% 20% Overall survival among patients with PS=2 21% 16% 18% Tumor response rate 19 17 18 Median time to progression, weeks 30% 28% 38% Overall survival Vinorelbine + Gemcitabine Gemcitabine Vinorelbine Outcome

130. Targeted Therapy for Non-small Cell Lung Cancer

132. Tumorigenic Pathways in the Cell Are Complex Sigma Aldrich, Inc., St. Louis, MO

134. EGFR Targeting Strategies in NSCLC

137. Anti-EGFR Strategies Signal transduction mAbs TKIs Ligand TKI K K Ligand Survival and metastasis mAb Cetuximab Gefitinib Erlotinib Ligand Cell death Ligand Protein synthesis K K K K K K Toxin conjugates Antisense Panitumumab mAb, monoclonal antibody; TKI, tyrosine kinase inhibitor. Adapted from Raymond E, et al. Drugs . 2000;60(suppl 1):15-23.

138. Monoclonal Anti-EGFR Antibodies

139. Monoclonal Anti-EGFR Antibodies Pao W, Miller VA. J Clin Oncol . 2005;23:2556-2568. EGFR

140. Monoclonal Antibodies Monoclonal Antibodies Under development mAb 80 Under development h-R3 (TheraCIM) Under development MDX-447 (HuMab-Mouse) Under development EMD-72000 (matuzumab) Under development ABX-EGF (panitumumab) Approved, refractory metastatic CRC, pancreatic, head and neck Cetuximab Status Agent

142. Phase II Trials of Cetuximab in Advanced NSCLC PR, partial response. 1. Rosell R, et al. Proc Am Soc Clin Oncol. 2004;23:618a; 2. Robert F, et al . J Clin Oncol . 2005;23:9089-9096; 3. Thienelt CD, et al. J Clin Oncol . 2005;23:8786-8793. Median Survival PR Patients, n Treatment Study No Prior Chemotherapy 11.0 months 26% 31 Cetuximab + paclitaxel + carboplatin Thienelt et al. 3 7.0 months 20% 43 Cetuximab + vinorelbine 10.3 months 28.6% 35 Cetuximab + gemcitabine + carboplatin Robert et al. 2 8.3 months 31.7% 43 Cetuximab + cisplatin + vinorelbine Rosell et al. 1

143. Phase II Trials of Cetuximab in Advanced NSCLC PR, partial response; TTP, time to progression. 1. Lynch TJ, et al. Proc Am Soc Clin Oncol . 2004;23:634a; 2. Kim ES, et al. Proc Am Soc Clin Oncol. 2003;22:642a. Median Survival PR Patients, n No. Prior Chemo Treatment Study Prior Chemotherapy TTP 3 months 28% 47 > 1 Cetuximab + docetaxel Kim et al. 2 7% 29 > 1 Cetuximab Lynch et al. 1

145. EGFR-targeted Agents: Small Molecule Tyrosine Kinase Inhibitors

146. Tyrosine Kinase Inhibitors Small molecule tyrosine kinase inhibitors Class Under development Under development Under development CI-1033 HKI 272 BIBW2922 Under development EKB-569 Approved for advanced NSCLC Erlotinib Approved for advanced NSCLC Gefitinib Status Agent

148. EGFR Tyrosine Kinase Inhibitors in Recurrent NSCLC Phase II Trials Assessing Second-line Treatment 1. Fukuoka M, et al. J Clin Oncol . 2003;21:2237-2246; 2. Kris MG, et al. JAMA . 2003; 290:2149-2158; 3. Perez-Soler R, et al. Proc Am Soc Clin Oncol . 2001;20:310a. Abstract. 18.7% N=210 Gefitinib Monotherapy 1 2.75 months Median progression-free survival 8.4 months 7.8 months Median overall survival 12.3% 10.3% Overall response rate N=57 N=216 Study population Erlotinib Monotherapy 3 Gefitinib Monotherapy 2 Parameter

149. Patient Characteristics Associated with Response Response to Second-line Treatment with Gefitinib Fukuoka M, et al. J Clin Oncol . 2003;21:2237-2246. Symptom Improvement Response Rate 30 4 Other 43 13 Adenocarcinoma 31 3 Men 49 19 Women 32 15 > 4 prior regimens 44 10 3 prior regimens 39 8 2 prior regimens 36 14 PS 2 40 9 PS 0-1 Rate (%) (%) Characteristic

151. ISEL Trial 709: Phase III Gefitinib in Second- or Third-line NSCLC (cont.) Adenocarcinoma All patients Female PS 0,1 1 prior chemo Refractory Never smoked Non-adenocarcinoma Ever smoked Intolerant 2 prior chemos PS 2,3 Male Hazard ratio and 95% CI Favors gefitinib Favors placebo 11.4% 7.7% 14.0% 8.3% 7.4% 7.8% 17.2% 4.6% 5.2% 7.2% 8.0% 6.6% 4.9% Survival Response Rate 0.4 0.6 0.8 1 1.5 Thatcher N, et al. Lancet . 2005;366:1527-1537.

153. Characteristics of Patients Responding to Gefitinib Lynch TJ, et al. N Engl J Med. 2004;350:2129-2139. Partial Partial Partial Major Partial Minor Partial Major Major Response No Yes Yes Yes Yes Yes Yes Yes Yes EGFR Mutation >33.5 17.9 >4.3 >7.8 >14.7 >21.4 12.9 >14.0 18.8 Overall Survival (mo) >33.5 11.7 >4.3 >7.8 >14.7 >13.3 9.6 >14.0 15.6 Duration of Therapy BAC Adeno Adeno BAC Adeno Adeno Adeno BAC BAC Pathological Type 42 58 62 32 45 81 64 66 70 Age F F F M F F M M F Sex 9 8 7 6 5 4 3 2 1 Patient Never 2 Former 1 Former 1 Never 3 Never 2 Former 1 Never 2 Never 0 Never 3 Smoker? Prior Regimens

157. Anti-EGFR Targeted Agents: EGFR Copy Number in NSCLC Hirsch FR, et al. J Clin Oncol . 2005;23:6838-6845; Cappuzzo F, et al. J Natl Cancer Inst . 2005;97:643-655. 0.072 0.042 P -value 4 months 9 months Median progression-free survival 8 months Not yet reached Median overall survival EGFR-FISH Negative EGFR-FISH Positive Outcome

160. BR.21 Trial: Overall Survival Shepherd FA, et al. N Engl J Med . 2005;353:123-132. No. at risk: Placebo 243 107 50 9 0 0 Erlotinib 488 255 145 23 1 0 HR=0.70 (95% CI, 0.58 to 0.85) P <0.001 by stratified log-rank test Erlotinib Placebo

161. BR.21 Trial: Progression-free Survival Shepherd FA, et al. N Engl J Med . 2005;353:123-132. No. at risk: Placebo 243 20 3 0 0 0 Erlotinib 488 115 27 2 1 0 HR=0.70 (95% CI, 0.58 to 0.85) P <0.001 by stratified log-rank test Erlotinib Placebo

162. BR.21 Trial: Outcomes Shepherd FA, et al. N Engl J Med . 2005;353:123-132. <0.001 1.8 2.2 Median PFS, mo <0.001 <1.0% 8.9% Response rate <0.001 4.7 6.7 Median overall survival, mo P -value Placebo Erlotinib Outcome

163. BR.21 Trial: Survival in Expressing vs Nonexpressing EGFR Patients Survival in EGFR-negative Patients 0 0.25 0.5 0.75 1 0 6 12 18 24 30 Survival time (months) Survival probability Survival in EGFR-positive Patients 0 0.25 0.5 0.75 1 0 6 12 18 24 30 Survival time (months) Survival probability Shepherd FA, et al. N Engl J Med . 2005;353:123-132. HR: 1.01 95% CI: 0.65 to 1.57 Erlotnib (N=74) Placebo (N=37) HR: 0.65 95% CI: 0.43 to 0.97 Erlotinib (N=78) Placebo (N=49)

164. BR.21 Trial: Survival in EGFR Unmeasured Patients Shepherd FA, et al. N Engl J Med . 2005;353:123-132. HR: 0.76 95% CI: 0.61 to 0.93 Survival in EGFR Unmeasured Patients 0 0.25 0.5 0.75 1 0 6 12 18 24 30 Survival time (months) Survival probability Erlotinib (N=336) Placebo (N=157)

168. EGFR Inhibitor-associated Rash Acneform rash on face Acneform rash on chest Paronychial inflammation

169. MD Anderson Prospective Treatment Algorithm Consider dermatology consultation for grade 3/4 symptoms. Kim ES. ASCO 2005 Poster Session. Abstract 5546. Perfume-, alcohol-, dye-free lotion applied bid Grade 2/4 NA Grade 1 Dry skin Antibiotics: minocycline hydrochloride 200 mg bid, d1; then 100 mg bid OR trimethoprim/sulfamethoxazole bid Grade 2/4 Grade 1 Grade 3/4 Grade 2 Grade 1 Severity Antibiotics: clindamycin gel for limited single areas; clindamycin lotion for multiple scattered areas Pustular/ papular rash Oral steroids: methylprednisolone Topical steroids: fluticasone propionate Hydrocortisone cream 1% Treatment Macular rash Type

170. MD Anderson Prospective Treatment Algorithm (cont.) Consider dermatology consultation for grade 3/4 symptoms. Kim ES. ASCO 2005 Poster Session. Abstract 5546. Silver sulfadiazine ointment Grade 4 Petroleum jelly or silver sulfadiazine ointment Grade 3 Grade 1/2 Grade 3/4 Grade 2 Grade 1 Severity NA Ulcerative lesions Antihistamine: diphenhydramine 25-50 mg PO q6 h prn OR hydroxyzine hydrochloride 25-50 mg PO q6 h prn Antihistamine: topical or oral diphenhydramine 25-50 mg q6 h prn OR hydroxyzine hydrochloride 25-50 mg PO q6 h prn NA Treatment Pruritus Type

172. EGFR Tyrosine Kinase Inhibitors Plus Chemotherapy Phase III Trials Assessing First-line Treatment 1. Giaccone G, et al. J Clin Oncol . 2004;22:777-784; 2. Herbst RS, et al. J Clin Oncol. 2004;22:785-794; 3. Herbst RS, et al. ASCO 2004;23:617; 4. Gatzemeier U, et al. ASCO 2004;23:617. Negative N=1172 Paclitaxel + carboplatin Erlotinib TALENT 4 Negative N=1059 Gemcitabine + cisplatin Erlotinib TRIBUTE 3 Negative N=1037 Paclitaxel + carboplatin Gefitinib INTACT 2 2 Negative N=1093 Gemcitabine + cisplatin Gefitinib INTACT 1 1 Outcome Study Population Chemotherapy Agent Trial

173. Additional TKIs of Interest Previously treated breast cancer, locally advanced or metastatic biliary tract or liver cancer, metastatic prostate cancer II Small-molecule ErbB-1 and ErbB-2 tyrosine kinase inhibitor Lapatinib Previously treated advanced ovarian cancer II Small-molecule EGFR tyrosine kinase inhibitor CI-1033 Previously treated advanced CRC II Small-molecule EGFR tyrosine kinase inhibitor EKB-569 Treatment Phase Class Compound

174. Angiogenesis-targeted Agents in NSCLC

176. VEGF Family and Its Receptors RTK, receptor tyrosine kinase. Dvorak HF. J Clin Oncol. 2002;20:4368; Ferrara N, et al. Nat Med. 2003;9:669. VEGFR-3 (Flt-4) VEGFR-2 (Flk-1/KDR) VEGFR-1 (Flt-1) Angiogenesis (RTK) Angiogenesis, lymphangiogenesis (RTK) Lymphangiogenesis (RTK) PIGF VEGF-A VEGF-B VEGF-C VEGF-D 0 0 0 0 0 NRP-1 (Neuropilin) Unclear, but likely involved in tumor growth (non-RTK)

177. Ligand sequestration: mAbs, soluble receptors (eg, bevacizumab) Receptor-blocking mAbs (eg, I MC-1121) Tyrosine kinase inhibition: TKIs (eg, SU11248) p85 PLC  GRB2 SOS ras Transcription factor inhibition VEGF Signal Inhibition VEGF VEGFR

179. VEGF Overexpression in Select Tumors Vascular density 30%-100% Renal cell Recurrence, survival, vascular density 30% Prostate Recurrence, survival 30%-60% Breast Recurrence, survival 40%-60% Colorectal Recurrence, survival 45%-55% NSCLC Correlation % of Tumors with VEGF Overexpression Tumor Type

180. Selected Agents Targeting the VEGF Ligand Phase I completed VEGF HuMV833 Agents Targeting the VEGF Ligand Phase III VEGF Bevacizumab Antibodies Phase I VEGF PlGF VEGF-Trap Soluble receptors Stage of Development Targets Examples Class

181. Selected Agents Targeting the VEGF Receptors Agents Targeting the VEGF Receptors Phase I VEGFR-2 IMC-1121 Antibodies Phase III VEGFR-1 Angiozyme Ribozymes Stage of Development Targets Examples Class

186. Phase II Bevacizumab Plus Chemotherapy in First-line NSCLC Johnson DH, et al. J Clin Oncol . 2004;22:2184-2191. 4.2 months 7.4 months 4.3 months Median time to progression 14.9 months 17.7 months 11.6 months Median overall survival 18.8% 31.5% 28.1% Response rate Control Arm Bevacizumab 15 mg/kg Bevacizumab 7.5 mg/kg Outcome

188. ECOG E4599: Median Survival Sandler AB, et al. ASCO 2005. Abstract LBA4. 12 mo 24 mo 43.7% 16.9% 51.9% 22.1% 0 0.2 0.4 0.6 0.8 1.0 Probability PC PCB P =0.007 0 6 12 18 24 30 36 Months Medians: 10.2, 12.5 HR: 0.77 (0.65, 0.93)

189. ECOG E4599: Results Sandler AB, et al. ASCO 2005. Abstract LBA4. <0.0001 4.5 months 6.4 months Median progression-free survival 0.0075 10.2 months 12.5 months Median overall survival <0.0001 10.0% 27.2% Overall response rate P -value Paclitaxel + Carboplatin Bevacizumab + Paclitaxel + Carboplatin Outcome

190. ECOG E4599: Toxicity *5 deaths due to hemoptysis, all in bevacizumab-treated arm. Sandler AB, et al. ASCO 2005. Abstract LBA4; Sandler AB, et al. ASCO 2006. Abstract 7068. 2 8 Deaths, n* <0.001 0.7% 6.0% Hypertension <0.01 0.0% 1.4% Grade 4 thrombocytopenia <0.01 16.4% 24.0% Grade 4 neutropenia <0.001 0.7% 4.5% Grade 3/4 hemorrhage P -value Paclitaxel + Carboplatin Bevacizumab + Paclitaxel + Carboplatin Outcome

194. Combining Bevacizumab and Erlotinib: Rationale

198. Antiangiogenic Tyrosine Kinase Inhibitors All agents in early phase I/I development except for PTK787 in phase III. + ? ? - + - AstraZeneca ZD6474 ? + + + + + Amgen AMG 706 ? + + + + + Pfizer AG013736 + + + - + - Pfizer SU11248 ? ? ? + + + GSK GW786034 ? ? ? + + + AstraZeneca AZD2171 ? + + + + + Novartis Schering PTK787 FGFR c-KIT PDGFR VEGFR-3 VEGFR-2 VEGFR-1 Company Inhibitor Target

201. Phase II Trial of ZD6474 vs Gefitinib: Progression-free Survival Natale R, et al. Chemotherapy Foundation Symposium XXIII 2005. HR=0.632 (95% CI=0.44 to 0.90) Two-sided P -value=0.011 Primary Endpoint: Progression-free Survival 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 1 2 3 4 5 6 7 8 9 10 11 Progression-free survival in part A (months) Probability of remaining Progression free ZD6474 Gefitinib

203. ZD6474 +/- Docetaxel: Progression-free Survival Kaplan-Meier Curve for Progression-free Survival 0 0.25 0.5 0.75 1 0 50 100 150 200 250 300 350 400 Progression-free survival (days) Survival distribution function Heymach R, et al. IASLC 11 th World Congress on Lung Cancer. 2005. Abstract 3023. Placebo + docetaxel ZD6474 100 mg + docetaxel ZD6474 300 mg + docetaxel Censored Censored Censored

210. Summary and Future Directions

214. Appendix

215. Adjuvant Therapy Supplement

216. ALPI: Effects of Mitomycin, Vindesine, and Cisplatin Adjuvant Chemotherapy Efficacy of Adjuvant Chemotherapy vs Observation Alone ALPI, Adjuvant Lung Project Italy. Scagliotti GV, et al. J Natl Cancer Inst. 2003;95:1453-1461. 1% 0.589 0.96 (0.81-1.13) Mitomycin + vindesine + cisplatin Absolute Benefit at 5 Years P -value Hazard Ratio (95% CI) Overall Survival by Therapy Type

217. ALPI: Effects of Mitomycin, Vindesine, and Cisplatin Adjuvant Chemotherapy (cont.) N=1088 patients with resected stage I, II, or IIIA NSCLC ALPI, Adjuvant Lung Project Italy. Scagliotti GV, et al. J Natl Cancer Inst. 2003;95:1453-1461. HR=0.87 (95% CI=0.81 to 1.13) P =0.589 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 1 2 3 4 5 Years from randomization Overall survival 540 289 Control 548 279 MVP Total Events

218. Treatment of Advanced NSCLC Supplement

219. FDA-approved Treatment for Advanced NSCLC 75 mg/m 2 day 1 every 3 weeks 75 mg/m 2 day 1 every 3 weeks 1250 mg/m 2 days 1 and 8 every 3 weeks 100 mg/m 2 after gemcitabine day 1 1000 mg/m 2 days 1, 8, and 15 every 4 weeks 100 mg/m 2 after gemcitabine day 1 30 mg/m 2 weekly 120 mg/m 2 days 1 and 19, then every 6 weeks 135 mg/m 2 over 24 h every 3 weeks 75 mg/m 2 after paclitaxel every 3 weeks Gemcitabine Cisplatin Vinorelbine Cisplatin Docetaxel Cisplatin Gemcitabine Cisplatin Paclitaxel Cisplatin

220. Second-line Therapy Studies 22 20 30 Gemcitabine 1000 mg/m 2 Gridelli, 1999 NR 14 22 Irinotecan 200 mg/m 2 Nakai, 1991 18 3 40 Paclitaxel 175 mg/m 2 Murphy, 1994 NR 17 35 Docetaxel 100 mg/m 2 Burris, 1993 NR 23 26 Paclitaxel 135 or 200 mg/m 2 Hainsworth, 1995 NR NR NR Median Survival (weeks) 8 35 0 Overall Response Rate (%) 22* 22+ Pemetrexed 500 mg/m 2 Mattson, 1999 18 Vinorelbine 20 mg/m 2 Rinaldi, 1994 N Dose/Schedule Study

221. Targeted Therapy Supplement

223. Inhibition of Xenograft Tumor Growth: Gefitinib with Paclitaxel Control Paclitaxel Gefitinib Gefitinib + paclitaxel Tumor mass (mg) LX-1 Lung 0 200 400 600 800 1000 1200 0 4 8 12 16 20 24 28 32 36 Time (days) Sirotnak FM, et al. Clin Cancer Res . 2000;6:4885-4892.

226. Antiangiogenic Targeted Agents: Biological Rationale Herbst RS, et al. J Clin Oncol. 2005;23:3243-3256.

229. Novel Cytotoxic Agents for the Treatment of NSCLC: Epothilones CR, complete response; ND, not determined; PR, partial response; SD, stable disease. Goodin S, et al. J Clin Oncol . 2004;22:2015-2025. Testicular, ovarian, pancreatic, and breast cancers ND I KOS-862 (epothilone D) Ovarian, prostate, breast, colorectal, and metastatic renal cell cancers ND II EPO906 Ovarian, bladder, stomach, and breast cancers 1 CR I BMS-310705 Metastatic gastric cancer, metastatic breast cancer, GI tract tumors 1 CR, 13 PR, and 31 SD in 111 assessable patients II BMS-247550 (aza-epothilone B) Other Cancers Tested Efficacy in NSCLC Patients Phase of Development Compound

230. Novel Cytotoxic Agents for the Treatment of NSCLC: Topoisomerase I Inhibitors 1. Baka S, et al. Eur J Cancer . 2005;41:1547-1550; 2. Braybrooke JP, et al. Lung Cancer . 2003;41:215-219; 3. Springett GM, et al. J Clin Oncol. 2004;22(14S):3127; 4. Miller AA, et al. Lung Cancer . 2005;48:399-407; Sigma Tau Research Data on file. 15 (38.5%) 2 (5.1%) 39 Exatecan Braybrooke et al. 2 4 (21.1%; includes 2 lung cancer patients) – 19 Polyglutamate camptothecin (CT-2106) Springett et al. 3 24 (46.1%) 2 (3.8%) 52 Karenitecin Miller et al. 4 Gimatecan Rubitecan Treatment First-line Treatment Second-line Treatment In phase I analysis 30 (planned) Sigma Tau Research 10 (58.8%) 0 (0%) 17 Baka et al. 1 Minor Response/ Stable Disease, n (%) Partial Response, n (%) Patients, n Study

232. Novel Agents: Bexarotene RXR, retinoid X receptors. 1. Khuri FR, et al. J Clin Oncol . 2001;19:2626-2637; 2. Rizvi NA, et al. ASCO 2002; Abstract 1334; 3. Bordoni R. ASCO 2006. Abstract 17070. Not given 16 (31%) 1 CR + 5 PR (40%) 30 (58%) 15 56 Bexarotene + paclitaxel + carboplatin Bexarotene + paclitaxel + carboplatin Rizvi et al. 2 Bordoni 3 14 (50%) 7 (25%) 28 Bexarotene + cisplatin + vinorelbine Khuri et al. 1 SD, n (%) PR, n (%) Patients, n Treatment Study