Lung Cancer: More than meets the eye

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1 Lung Cancer Education Program November 23, 2013 Lung Cancer: More than meets the eye Shantanu Banerji MD, FRCPC

2 Presenter Disclosure Faculty: Shantanu Banerji Relationships with commercial interests: Grants/Research Support: CancerCare Manitoba Foundation Speakers Bureau/Honoraria: AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Pfizer Consulting Fees: None Other: Employee of CancerCare Manitoba

3 Mitigating Potential Bias Will not be talking about any off label use of drugs Only speak abut drugs approved for use in Manitoba

4 Outline Overview of lung cancer demographics Define lung cancer subtypes Clinical level Molecular Level

5 Canadian Cancer Statistics 2013 Incidence Mortality Canadian Cancer Society

6 Changing Demographics

7 Annual percent change in age-standardized mortality rate for selected cancers, by sex, Canada, All cancers Hodgkin lymphoma Males Females Cervix Stomach Larynx Prostate Oral Non-Hodgkin lymphoma Testis Lung Breast Multiple myeloma Colorectal Brain Leukemia Kidney Pancreas Body of Uterus Bladder Ovary Esophagus APC starts from changepoint year for the APC starts from changepoint following year cancer for the types: following cancer types: All cancers (males) 2001 All cancers (males) 2001 Colorectal (males) 2003 Larynx (males) 2001 Non-Hodgkin lymphoma (males & females) 2000 Prostate (males) 2001 Prostate (males) 2001 Non-Hodgkin lymphoma (males) 2001 Ovary 2003 Non-Hodgkin lymphoma (females) 2000 Breast (females) 2002 Melanoma Thyroid Liver decreasing % annual change increasing Data source: Canadian Cancer Statistics 2012

8 Risk Factors Tobacco smoke Environmental radiation Air pollution Chronic lung diseases Chronic infection Asbestos

9 Major Subtypes of Lung Cancer 1. Non-small cell lung cancer (85%) Adenocarcinoma (50%) Squamous cell (20%) Large cell (<10%) Undefined (20-30%) 2. Small cell carcinoma (13-15%) 3. Mesothelioma (<1%)

10 Adenocarcinoma Large cell Squamous cell Glandular architecture Neuroendocrine features Keratinization Non-small cell lung cancer

11 Non-Small Cell Lung Cancer Arise from epithelial cells in the lung and airways May occur in non-smokers (mainly adenocarcinoma) Can be cured with surgery or radiation for early stages of disease Less sensitive to radiation and chemotherapy than SCLC (30-40% response rates to chemo)

12 NSCLC Staging Stage I Stage II Stage III

13 Stage IV NSCLC

14 Treatment algorithm (2004)

15 NSCLC 5-year survival by Stage MST without treatment for Stage IV disease is 4-6 months Colon Cancer Breast Cancer American Cancer Society

16 Erlotinib in Second and Third line Abcam.com Shepherd et al. NEJM 2005; 353:123-32

17 Pemetrexed in second line Hanna et al. J Clin Oncol 2004;22:

18 Pemetrexedis only effective in nonsquamous NSCLC Chen. Lung Cancer Oct;74(1):132-8 Takezawa. British Journal of Cancer (2010) 103,

19 Early Palliative Care Temel et al., NEJM, 2010

20 Lung Cancer is a Heterogeneous Disease PNAS Nov 20;98(24):

21 EGFR Mutations in Adenocarcinoma Clinical Predictors of Response Female Non-smoker Asian ethnicity Lynch. N Engl J Med 2004; 350: Mitsudomi. J Clin Oncol Apr 10;23(11):

22 Targeted therapy can be used as first line therapy only in the appropriate genetic context Probability of PFS Carboplatin/ paclitaxel EGFR M+ 9.5 m 6.3 m 0.48 CI 0.36, 0.64, p< EGFR M- 1.5 m 5.5 m 2.85 CI 2.05, 3.98, p< HR Time from randomisation (months) Mok. N Engl J Med 2009;361:

23 Targeting the ALK fusion No. at risk Crizotinib Chemotherapy Time (months)

24 Lung cancer in never smokers Sun et al. Nature Rev Cancer, 2007

25 Treatment algorithm (2013)

26 Improved therapy has led to survival gains for Stage IV NSCLC Third line therapy (2000+) Second line chemotherapy or targeted therapy (2000+) Standard First platinum-based line targeted chemotherapy (1990 s) (2009+) Best Supportive Care (pre-1990 s) Quality of Life Median Survival (months)

27 The personalization of cancer care Adenocarcinoma Large cell Squamous cell

28 The diagnosis of cancer is becoming more complex Re-biopsy Combination therapies

29 Next-generation technologies

30 Small cell lung cancer

31 Small Cell Lung Cancer Arises from neuro-endocrine cells Most associated with smoking Most aggressive lung cancer variant (MST without treatment 4-6 weeks) Most responsive to chemotherapy (70%) Treat patients with poor performance (MST with treatment 4-6 months) Almost all patients will relapse within weeks to months Associated with paraneoplastic syndromes SIADH Cushing s Eaton-Lambert Cerebellar degeneration Cachexia

32 Staging and Survival Stage I Stage II Stage III Stage IV Limited Stage Extensive Stage 5-year relative survival

33 Therapeutic course Initial Treatment: 4 cycle cis/etop May go to 6 cycles if Started at sub-therapeutic doses Good response but still some residual disease after 4 cycles Tolerating well Disease progression: Within 3 months will not respond to any other chemotherapy Within 3-6 months may respond to second line agents (<20% RR) > 6 months ay respond to initial platinum doublet (40% RR)

34 mesothelioma

35 Mesothelioma Arises from the mesothelial lining of the pleura Most commonly associated with asbestos exposure (often appears 20+ years after exposure) Patients can often live several years after diagnosis Treatment: Surgery restricted to very small disease Radiation mainly to palliate symptoms Chemotherapy only treatment that prolongs survival First line therapy cisplatinum and pemetrexed Second line gemcitabine Multi-modality therapy currently being studied

36 Summary Lung caner in women and non-smokers is rising Treatment of NSCLC is more complex than ever Personalized therapy depends on histology and genotype of lung tumours Outcomes dependent on type of lung cancer

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