New Options for Achieving Individualized Approaches to Non-Small Cell Lung Cancer (NSCLC) Management

New Options for Achieving Individualized Approaches to Non-Small Cell Lung Cancer (NSCLC) Management Ramaswamy Govindan, MD Director Professor of Medicine Director, Thoracic Oncology Program Department of Internal Medicine, Division of Oncology Washington University School of Medicine St. Louis, Missouri

Faculty Disclosure It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity. Dr. Govindan has received grants/research support from Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Lilly Oncology, and Pfizer.

Educational Activity Learning Objectives List barriers that hinder optimal care for NSCLC patients and establish methods to achieve improved outcomes Define strategies to better include patients and their families in a shared decision making process for the management of their NSCLC Assess the latest data from newer oncologic therapies to determine future strategies for improving the significant failure rate seen among current approaches for NSCLC management Determine individualized NSCLC patient scenarios where novel targeted therapies may apply and assess how these options may integrate into existing regimens, taking into account potential safety issues Examine the potential role of biomarkers in the individualized management of NSCLC patients and identify new knowledge and skill sets required for their incorporation into clinical practice

Estimated New Cancer Cases United States, 2009 Males Females Jemal A, et al. CA Cancer J Clin. 2009;59(4):225-249.

Estimated Cancer Deaths United States, 2009 Males Females Jemal A, et al. CA Cancer J Clin. 2009;59(4):225-249.

Non-small Cell Lung Cancer (NSCLC) NSCLC accounts for ~135,000 cases of lung cancer annually Approximately 30 40% of these patients will have metastatic disease Untreated patients have a median survival of ~4 5 months

> 85% of Lung Cancer Is Caused by Cigarette Smoking Decrease in risk seen 5 years after stopping, never reaches baseline Cessation after diagnosis improves treatment tolerance and outcome Videtic GM, et al. J Clin Oncol. 2003;21(8):1544-1549. Fox JL, et al. Lung Cancer. 2004;44(3):287-293.

Survival by Clinical and Pathologic Stage Proposed IASLC Stage Groupings IASLC = International Association for the Study of Lung Cancer Detterbeck FC, et al. Chest. 2009;136:260-271. Goldstraw P, et al. J Thorac Oncol. 2007;2:706-714.

Lung Cancer: Symptoms Related to Primary Lesion Cough, often dry Shortness of breath Hemoptysis Wheezing Related to Spread within Chest Shortness of breath Hoarseness Superior vena cava syndrome Horner s syndrome Related to Distant Metastasis Brain Bone Liver Adrenal glands

Lung Cancer Assessment History and Physical Exam Assess weight loss Performance status Labs: CBC, comprehensive metabolic panel Smoking cessation counseling CXR CT Chest with IV contrast (includes liver and adrenal glands) Biopsy Bronchoscopy CT guided Mediastinoscopy Endoscopic ultrasonography Thoracentesis +/- FDG-PET scan +/- MRI Brain/Spine

Overview of NSCLC Treatment Stage I Stage II Stage III Stage IV or Recurrent Disease Surgery (Radiation if inoperable) Surgery With Adjuvant Chemotherapy Surgery or Radiation With Chemotherapy Chemotherapy Targeted Therapy

Non-Small Cell Lung Cancer: Stage IV Disease General Principles Baseline factors predict survival Weight loss Gender Performance status Age does not predict worse outcome Elderly patients with a good performance status should be offered systemic treatment Older patients are more susceptible to toxic side effects of chemotherapy

Survival with Cytotoxic Chemotherapies Delbaldo C, et al. JAMA. 2004;292:470-484. 2 drugs are better than 1

Survival with Cytotoxic Chemotherapies Delbaldo C, et al. JAMA. 2004;292:470-484. 3 cytotoxic drugs are not better than 2

Cis/Gem vs Cis/Pemetrexed Randomization Factors Stage Performance status Gender Histologic vs cytologic diagnosis History of brain metastases R A N D O M I Z A T I O N Vitamin B 12, folate, and dexamethasone given in both arms Cisplatin 75 mg/m 2 day 1 + Gemcitabine 1250 mg/m 2 days 1,8 (n = 863) Each cycle repeated q 3 wk up to 6 cycles Cisplatin 75 mg/m 2 day 1 + Pemetrexed 500 mg/m 2 day 1 (n = 862) Primary Endpoint Overall Survival Scagliotti GV, et al. J Clin Oncol. 2008;26(21):3543-3551.

Survival Probability Cis/Gem vs Cis/Pemetrexed: Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Median (95% CI) Cisplatin/pemetrexed 10.3 (9.8-11.2) Cisplatin/gemcitabine 10.3 (9.6-10.9) CP vs CG Adjusted HR (95% CI) 0 6 12 18 24 30 Survival Time, mo 0.94 (0.84-1.05) Scagliotti GV, et al. J Clin Oncol. 2008;26(21):3543-3551.

Survival Probability Cis/Gem vs Cis/Pemetrexed: Survival in Nonsquamous Carcinoma 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Median (95% CI) Cisplatin/pemetrexed 11.8 (10.4, 13.2) Cisplatin/gemcitabine 10.4 (9.6, 11.2) CP vs CG 0 6 12 18 24 30 Adjusted HR (95% CI) 0.81 (0.70-0.94) Survival Time in Patients With Nonsquamous Histology, mo Scagliotti GV, et al. J Clin Oncol. 2008;26(21):3543-3551.

Pre-specified Histology Analysis Histology Subgroup Median Overall Survival in Months (95% CI) Unadjusted Hazard Ratio Cisplatin/ Pemetrexed Cisplatin/ Gemcitabine (HR) a,b (95% CI) Adjusted Hazard Ratio (HR) a,b,c (95% CI) Nonsquamous NSCLC d (N = 1252) Adenocarcinoma (N = 847) 11.0 (10.1-12.5) 12.6 (10.7-13.6) N = 618 N = 436 10.1 (9.3-10.9) 10.9 (10.2-11.9) N = 634 N = 411 0.84 (0.74-0.96) 0.84 (0.71-0.98) 0.84 (0.74-0.96) 0.84 (0.71-0.99) Large Cell (N = 153) 10.4 (8.6-14.1) N = 76 6.7 (5.5-9.0) N = 77 0.68 (0.48-0.97) 0.67 (0.48-0.96) Other e (N = 252) 8.6 (6.8-10.2) N = 106 9.2 (8.1-10.6) N = 146 1.12 (0.84-1.49) 1.08 (0.81-1.45) Squamous Cell NSCLC (N = 473) 9.4 (8.4-10.2) N = 244 10.8 (9.5-12.1) N = 229 1.22 (0.99-1.50) 1.23 (1.00-1.51) a An HR that is less than 1.0 indicates that survival is better in the AC arm than in the GC arm. Alternatively, an HR that is greater than 1.0 indicates survival is better in the GC arm than in the AC arm. b Unadjusted for multiple comparisons c HRs adjusted for ECOG PS, gender, disease stage, and basis for pathological diagnosis (histopathological/cytopathological) d Included adenocarcinoma, large cell, and other histologies except those with squamous cell type e The subgroup of other represents patients with primary diagnosis of NSCLC whose disease did not clearly qualify as adenocarcinoma, squamous cell carcinoma, or large cell carcinoma. Scagliotti GV, et al. J Clin Oncol. 2008;26(21):3543-3551.

Maintenance Pemetrexed vs Placebo Pemetrexed + BSC (N = 441)* Stage IIIB/IV NSCLC ECOG PS 0-1 4 prior cycles of gem, doce, or tax + cis or carbo, with CR, PR, or SD 2:1 Randomization Primary Endpoint = PFS Placebo (d1, q21d) + BSC (N = 222)* Ciuleanu T, et al. Lancet. 2009;374(9699):1432-1440.

PFS Probability Progression-free Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 HR = 0.60 (95% CI: 0.49 0.73) P < 0.00001 Pemetrexed 4.0 mos Placebo 2.0 mos 0 3 6 9 12 15 18 21 24 Time (months) Ciuleanu T, et al. Lancet. 2009;374(9699):1432-1440.

Survival Probability Overall Survival (ITT) 1.0 HR = 0.79 (95% CI: 0.65 0.95) P = 0.012 0.9 0.8 0.7 0.6 0.5 Pemetrexed 13.4 mos 0.4 0.3 Placebo 10.6 mos 0.2 0.1 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Time (months) Ciuleanu T, et al. Lancet. 2009;374(9699):1432-1440.

Survival Probability Overall Survival Adenocarcinoma Adenocarcinoma (n = 481) 1.0 HR = 0.70 (95% CI: 0.56-0.88) P = 0.002 0.9 0.8 0.7 0.6 0.5 0.4 Pemetrexed 15.5 mos 0.3 0.2 0.1 0.0 Placebo 10.3 mos 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Time (months) Ciuleanu T, et al. Lancet. 2009;374(9699):1432-1440.

Targeted Therapy in Oncology Target Present in tumor tissue Critical for tumor growth/progression Druggable Dispensable or absent in normal cells Drug Discovery and Development Agent Targets tumor cells Spares normal cells Decreased toxicity

Agents Targeting the VEGF Pathway Anti-VEGF antibodies (bevacizumab) VEGF Soluble VEGFRs (VEGF-Trap) P P P P VEGFR-1 P P P P VEGFR-2 Anti-VEGFR antibodies (IMC-1121b) Podar K, Anderson K. Blood. 2005;105(4):1383-1395. Endothelial cell Small-molecule VEGFR inhibitors Vatalanib (PTK 787) Sunitinib (SU11248) Sorafenib (Bay 43-9006) ZD6474

Phase III Trial of Bevacizumab in Non-Squamous NSCLC: ECOG 4599 N = 855 (eligible) Eligibility: Non-squamous NSCLC No Hx of hemoptysis No CNS metastases Stratification Variables: RT vs no RT Stage IIIB or IV vs recurrent Wt loss < 5% vs 5% Measurable vs non-measurable Sandler A, et al. New Engl J Med. 2006;355(24):2542-2550. (PC) Paclitaxel 200 mg/m 2 Carboplatin AUC = 6 (q 3 weeks) x 6 cycles (PCB) PC x 6 cycles + Bevacizumab (15 mg/kg q 3 wks) to PD No crossover to bevacizumab permitted

Patients With PFS (%) Patients Surviving (%) 100 80 60 40 Carboplatin/Paclitaxel +/- Bevacizumab: Key Clinical Outcomes Progression-Free Survival Carboplatin/paclitaxel Carboplatin/paclitaxel + bevacizumab P < 0.001; HR = 0.66 Median PFS: 6.2 months vs 4.5 months 6-Month PFS: 55% vs 33% 1-Year PFS: 15% vs 6% 100 80 60 40 Overall Survival Carboplatin/paclitaxel Carboplatin/paclitaxel + bevacizumab P = 0.003; HR = 0.79 Median OS: 12.3 months vs 10.3 months 1-Year OS: 51% vs 44% 2-Year OS: 23% vs 15% 20 0 0 6 12 18 24 30 36 Months 20 0 0 6 12 18 24 30 36 Months HR = hazard ratio; OS = overall survival; PFS = progression-free survival Response rate = carboplatin/paclitaxel 15%; carboplatin/paclitaxel + bevacizumab 35%; P < 0.001 Sandler A, et al. N Engl J Med. 2006;355(24):2542-2550. Sandler A, et al. J Clin Oncol. 2005;23(16S):4.

Grade 3 5 Non-Hematologic Toxicity CP (N = 441) BvCP (N = 427) P Value Hemorrhage 1.1 4.7 0.001 Hemoptysis 0.5% 2.1% CNS 0.2% 0.7% GI 0.5% 1.2% Other 0.2% 1.2% Hypertension 0.7% 7.7% < 0.001 Proteinuria --- 3.1% < 0.001 Venous thromb 3.2% 5.6% Arterial thromb 1.6% 2.8% Sandler A, et al. New Engl J Med. 2006;355(24):2542-2550.

AVAiL Trial Study Design Previously untreated, stage IIIb, IV or recurrent non-squamous NSCLC R A N D O M I Z E 2 1 1 2 Bevacizumab 7.5 mg/kg + CG Placebo 7.5 + CG Placebo 15 + CG Bevacizumab 15 mg/kg + CG Bevacizumab Bevacizumab PD PD PD Stratification factors: disease stage, ECOG, PS, region, gender Reck M, et al. J Clin Oncol. 2009;27(8):1227-1234. CG: cisplatin-gemcitabine

AVAiL Primary Endpoint: PFS Bevacizumab 7.5 mg Group Bevacizumab 15 mg Group Toxicity was similar to that of E4599 Reck M, et al. J Clin Oncol. 2009;27(8):1227-1234. CG: cisplatin-gemcitabine

Probability of OS 1.0 0.8 0.6 AVAiL: Overall Survival (secondary endpoint) HR (95% CI) Placebo + CG Bev 7.5 mg/kg + CG 0.93 (0.78 1.11) Bev 15 mg/kg + CG 1.03 (0.86 1.23) P value 0.42 0.76 Median OS (months) 13.1 13.6 13.4 0.4 0.2 No. at risk Placebo + CG Bev 7.5 mg/kg + CG Bev 15 mg/kg + CG 0 0 6 12 18 24 30 36 Time (months) 347 272 182 100 36 3 0 345 286 182 107 34 3 0 351 264 177 92 33 2 0 Reck M, et al. Ann Oncol. 2010 Feb 11. [Epub ahead of print] ITT (intent-to-treat) population CG: cisplatin-gemcitabine

Oral VEGF-TKIs Agent Target/MOA Company ZD6474 VEGFR-2, EGFR AstraZeneca Sunitinib VEGFR-1/2, PDGFR, Kit, FLT-3 Sugen/Pfizer Inc Sorafenib VEGFR-2/3, FLT-3, Kit Onyx/Bayer Vatalanib VEGFR-1/2/3, PDGFR, Kit Novartis AG013736 VEGFR-1/2, PDGFR, Kit Pfizer Inc AMG 706 VEGFR, PDGFR, Kit, Ret Amgen AEE-788 VEGFR, EGFR, erb Novartis

Adenocarcinoma Molecular Subtypes Pending

Adenocarcinoma Molecular Subtypes KRAS Pending EGFR BRAF PIK3CA MEK FGFR4 EML4-ALK HER2

EGFR Signaling gefitinib erlotinib Adapted from Ciardiello F, Tortora G. N Engl J Med. 2008;358:1160-1174.

EGFR Mutations Found in 350 of 2105 patients with advanced NSCLC(16.6%) Mutation distribution Women > men (70% vs 30%) Never smokers > smoking history (67% vs 33%) Those with adenocarcinomas (80.9%) (P < 0.001 for all comparisons) Deletions in exon 19 (62.2%) and L858R (37.8%) Adverse events Mild rashes Diarrhea Grade 3 cutaneous toxic effects in 16 patients (7.4%) Grade 3 diarrhea in 8 patients (3.7%) Rosell R, et al; Spanish Lung Cancer Group. N Engl J Med. 2009;361(10):958-967.

EGFR Mutations Rosell R, et al; Spanish Lung Cancer Group. N Engl J Med. 2009;361(10):958-967.

IPASS Study Design Patients Chemonaïve Age 18 years Adenocarcinoma histology Never or light exsmokers Life expectancy 12 weeks PS 0-2 Measurable stage IIIB/ IV disease Gefitinib (250 mg/day) 1:1 randomization Carboplatin (AUC 5 or 6) / paclitaxel (200 mg/m 2 ) 3 weekly Endpoints Primary Progression-free survival (non-inferiority) Secondary Objective response rate Overall survival Exploratory EGFR mutation Mok TS, et al. N Engl J Med. 2009;361(10):947-957.

Mok TS, et al. N Engl J Med. 2009;361(10):947-957. First-line Gefitinib vs Carboplatin-Paclitaxel

Mok TS, et al. N Engl J Med. 2009;361(10):947-957. First-line Gefitinib vs Carboplatin-Paclitaxel

Mechanisms of TKI Resistance TKI Sensitive Acquired Resistance 50% 20% Poor Initial Response Gazdar AF. Cancer Metastasis Rev. 2010;29(1):37-48.

Irreversible EGFR Inhibitors EGFR HER2 HER4 Clinical IC 50, nm IC 50, nm IC 50, nm Phase BIBW 2992 0.5 14 3 PF00299804 6 46 74 3 HKI-272 92 59 2 Doebele RC, et al. Lung Cancer. 2010 Jan 19. [Epub ahead of print]

Management of Cutaneous Toxicities Associated With EGFR Inhibitors Employ a proactive approach in managing skin reactions Suggest that patients use a thick, alcohol-free emollient cream Suggest that patients use a sunscreen of SPF 15 or higher, preferably containing zinc oxide or titanium dioxide If patient presents with rash, verify appropriate administration of drug* and proceed with the following therapy algorithm *Patient should be taking the drug on an empty stomach at the same time each day Lynch TJ, et al. Oncologist. 2007;12(5):610-621.

Proposed Therapy Algorithm for the Management of Cutaneous Toxicities Associated With EGFR Inhibitors The use of topical steroids should be employed in a pulse manner based on your institution s guidelines Lynch TJ, et al. Oncologist. 2007;12(5):610-621.

EML4-ALK Fusion Product in NSCLC A receptor tyrosine kinase (anaplastic lymphoma kinase [ALK] fuses to the echinoderm microtubule-associated protein-like 4 (EML-4) Multiple variants of the translocation have been identified Oncogenic (transforms cell lines and transgenic mice develop lung cancer) EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined Soda M, et al. Nature. 2007;448(7153):561-566.

Frequency of EML4/ALK Translocations Author Total Number Pos % Notes Shaw ASCO 2009 Inamura, JTO 2008 Takeuchi, CCR 2008 Koivuner, CCR 2008 Wong, Cancer 2009 Takahashi, ASO 2009 141 19 13% More likely in adenocarcinoma, light or never smokers, didn t overlap with EGFR or KRAS, younger patients 149 5 3% No overlap with EGFR or KRAS 253 11 4% 305 8 3% More common in never or light smokers 266 13 5% Mostly adenocarcinoma, never smokers, younger 313 5 1.6% Only looked at surgical cases. No overlap with EGFR, KRAS, HER2, 4 never smokers, 1 < 1py smoker, all adenocarcinomas.

Is the EML4-ALK Transcript Specific for NSCLC? PCR in 120 NSCLC specimens 1 Controls: Non-neoplastic lung tissues ALK protein levels assayed from 662 NSCLC specimens Results EML4-ALK transcripts (variants 1 and 3) detected in 9/120 NSCLC samples Also found in noncancerous lung tissues No transcripts were detected in matching tumor samples from these patients Analysis of EML4-ALK+ cases Only a minority of cells harbored the EML4-ALK gene (FISH) None of these cases was found to express the EML4-ALK protein Conclusion: EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC Findings challenged by Mano et al 2 Martelli MP, et al. Am J Pathol. 2009;174:661-670. Mano H, Takeuchi K. Am J Pathol. 2010 Jan 14. [Epub ahead of print]

Tumor Responses to PF-02341066 for NSCLC Evaluable Patients With ALK Fusions Tumor Size Change Duration of Response (Weeks) Kwak EL, et al. ASCO. 2009.

Molecular Analysis and NSCLC ERCC1 (excision repair cross complementation) Expression prognostic for improved survival Expression predictive of reduced response to platinum-based therapy RRM1 (regulatory subunit of ribonucleotide reductase) Expression prognostic for improved survival Expression predictive of reduced response to gemcitabine therapy BRCA1 (breast cancer 1) Low level of expression prognostic for long survival Low level of expression may be predictive of good platinum efficacy and poor taxane efficacy EGFR (epidermal growth factor receptor) EGFR mutations and gene copy number prognostic of survival Predictive for EGFR tyrosine kinase inhibitor efficacy Oligonucleotide-based Gene Expression Profiles Promising strategy for risk assessment and prediction of therapeutic efficacy Bepler G, et al. Cancer Control. 2008;15(2):130-139.

NSCLC Management Guidelines 1 Recommendations for the treatment of patients with stage IV NSCLC, based on 162 publications Chemotherapy and biologicals Strategies that improve overall survival First-line therapy Patients with performance status of 0 or 1 Platinum-based two-drug combination of cytotoxic drugs is recommended Nonplatinum cytotoxic doublets are acceptable for patients with contraindications For patients with performance status of 2, single cytotoxic drug is sufficient Azzoli CG, et al. J Clin Oncol. 2009;27(36):6251-6266.

NSCLC Management Guidelines 2 Stop first-line cytotoxic chemotherapy at disease progression or after 4 cycles in patients who are not responding to treatment Stop two-drug cytotoxic chemotherapy at 6 cycles in all patients EGFR mutations First-line gefitinib may be recommended for patients with known mutation Otherwise, cytotoxic chemotherapy is preferred Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry Bevacizumab is generally recommended with carboplatin-paclitaxel Second-line therapy Docetaxel Erlotinib Gefitinib or Pemetrexed Third-line therapy Erlotinib for erlotinib or gefitinib naive patients Data are insufficient to recommend the routine third-line use of cytotoxic drugs Data are insufficient to recommend routine use of molecular markers to select chemotherapy Azzoli CG, et al. J Clin Oncol. 2009;27(36):6251-6266.

Nursing Considerations Assessment Geriatric Patient Planning Histology, Stage, Intervention Patient Education Knowledge base Caregiver Support Resources

Multidisciplinary Patient Management Oncologists Nurses Thoracic surgeons Pulmonologists Pathologists Pharmacists Medical directors Case managers

Communication With Patients Goals Compliance (especially with po medications) Smoking cessation Patient self evaluation and reporting Manage disease symptoms, disease burden, and treatment side effects Offer Web resources

Case Scenario 1 55-year-old person with Stage IV NSCLC Adenocarcinoma histology Good performance status Hemoptysis on 3 occasions, total ~15 cc blood What is the most appropriate chemotherapy? A. Cisplatin and gemcitabine B. Cisplatin and pemetrexed C. Carboplatin, paclitaxel, bevacizumab D. Carboplatin and paclitaxel E. Cisplatin, vinorelbine, cetuximab

Case Scenario 1 55-year-old person with Stage IV NSCLC Adenocarcinoma histology Good performance status Hemoptysis on 3 occasions, total ~15 cc blood What is the most appropriate chemotherapy? Cisplatin and gemcitabine Cisplatin and pemetrexed B. Carboplatin, paclitaxel, bevacizumab Carboplatin and paclitaxel Cisplatin, vinorelbine, cetuximab

Case Scenario 2 55-year-old woman with Stage IV NSCLC Adenocarcinoma Good performance status EGFR exon 19 deletion What is the optimal chemotherapy? A. Carboplatin, paclitaxel, bevacizumab B. Carboplatin, paclitaxel C. Cisplatin, pemetrexed, bevacizumab D. Erlotinib

Case Scenario 2 55-year-old woman with Stage IV NSCLC Adenocarcinoma Good performance status EGFR exon 19 deletion What is the optimal chemotherapy? A. Carboplatin, paclitaxel, bevacizumab B. Carboplatin, paclitaxel C. Cisplatin, pemetrexed, bevacizumab Erlotinib

Case Scenario 3 55-year-old woman with Stage IV adenocarcinoma of the lung, completes 6 cycles of cisplatin, pemetrexed, and bevacizumab with stable disease, grade 1 neuropathy, and continues to work full time What is the most appropriate next step? A. Continue cisplatin, pemetrexed, and bevacizumab until progression B. Continue pemetrexed and bevacizumab until progression C. Continue bevacizumab until progression D. Continue pemetrexed until progression E. Discontinue therapy and monitor until progressive disease

Case Scenario 3 55-year-old woman with Stage IV adenocarcinoma of the lung, completes 6 cycles of cisplatin, pemetrexed, and bevacizumab with stable disease, grade 1 neuropathy, and continues to work full time What is the most appropriate next step? Continue cisplatin, pemetrexed, and bevacizumab until progression Continue pemetrexed and bevacizumab until progression Continue bevacizumab until progression Continue pemetrexed until progression Discontinue therapy and monitor until progressive disease

Case Scenario 4 55-year-old man with Stage IV squamous cell carcinoma completes 6 cycles of cisplatin and vinorelbine with stable disease, grade 1 neuropathy, and continues to work full time What is the most appropriate next step? Continue cisplatin and vinorelbine until progression Start erlotinib and continue until progression Start docetaxel and continue until progression Continue gemcitabine until progression Discontinue therapy and monitor until progressive disease

Case Scenario 4 55-year-old man with Stage IV squamous cell carcinoma completes 6 cycles of cisplatin and vinorelbine with stable disease, grade 1 neuropathy, and continues to work full time What is the most appropriate next step? Continue cisplatin and vinorelbine until progression Start erlotinib and continue until progression Start docetaxel and continue until progression Continue gemcitabine until progression Discontinue therapy and monitor until progressive disease

Summary Chemotherapy Two agents > one Three agents can be better than two Role for maintenance therapy? Still under evaluation Targeted Therapy Agents targeting the EGFR and VEGF pathways have proved successful Further study will include Earlier stage NSCLC Promising therapies are in development

Molecular targeting of cancer:

Lung Cancer: Conclusions Smoking remains primary cause of lung cancer Screening remains controversial Staging helps determine treatment Clinical trial participation may be attractive Multiple options in non-small cell lung cancer The Future: treat lung cancer based on molecular characteristics of tumors