An Interactive Guide to ALK+ Lymphoma. Our understanding of lung cancer has changed From one disease to many subtypes LCD

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1 An Interactive Guide to ALK+ Anaplastic Lymphoma Kinase Non-Small Cell Lung (NSCLC) Our understanding of lung cancer has changed From one disease to many subtypes Click to get started

2 Learning about Lung : How ALK+ NSCLC Fits In Lung cancer is the leading cause of cancer death worldwide in both men and women 1. In the United States alone an estimated 224,210 new cases of lung cancer are estimated to be diagnosed in 2014, accounting for 13% of total cancer diagnosis 2. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85-90% of cases, and adenocarcinoma is the most common type of NSCLC % of NSCLC cases are driven by a rearrangement of the anaplastic lymphoma kinase (ALK) gene 3. which is true or false Select from the options below. GENETIC SUBTYPES Click the lungs below to learn more. More people die of lung cancer in the U.S. than of colon, breast, pancreatic and prostate cancers combined 2,4. Not all lung cancers are the same. TRUE or FALSe TRUE or FALSe 1. American Society. Facts & Figures American Society. Accessed February 3, American Society. Detailed Guide: Lung (Non-Small Cell). American Society. org/acs/groups/cid/documents/webcontent/ pdf.pdf. Accessed February 3, National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Facts and Figures, American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012;

3 Learning about Lung : How ALK+ NSCLC Fits In Lung cancer is the leading cause of cancer death worldwide in both men and women 1. In the United States alone an estimated 224,210 new cases of lung cancer are estimated to be diagnosed in 2014, accounting for 13% of total cancer diagnosis 2. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85-90% of cases, and adenocarcinoma is the most common type of NSCLC % of NSCLC cases are driven by a rearrangement of the anaplastic lymphoma kinase (ALK) gene 3. which is true or false Select from the options below. GENETIC SUBTYPES Click the lungs below to learn more. More people die of lung cancer in the U.S. than of colon, breast, pancreatic and prostate cancers combined 2,4. Not all lung cancers are the same. TRUE or FALSe TRUE or FALSe TRUE 1. American Society. Facts & Figures American Society. Accessed February 3, American Society. Detailed Guide: Lung (Non-Small Cell). American Society. org/acs/groups/cid/documents/webcontent/ pdf.pdf. Accessed February 3, National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Facts and Figures, American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012;

4 Learning about Lung : How ALK+ NSCLC Fits In Lung cancer is the leading cause of cancer death worldwide in both men and women 1. In the United States alone an estimated 224,210 new cases of lung cancer are estimated to be diagnosed in 2014, accounting for 13% of total cancer diagnosis 2. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85-90% of cases, and adenocarcinoma is the most common type of NSCLC % of NSCLC cases are driven by a rearrangement of the anaplastic lymphoma kinase (ALK) gene 3. which is true or false Select from the options below. GENETIC SUBTYPES Click the lungs below to learn more. More people die of lung cancer in the U.S. than of colon, breast, pancreatic and prostate cancers combined 2,4. Not all lung cancers are the same. TRUE or FALSe TRUE or FALSe TRUE There are many subtypes based on different underlying genetic abnormalities, such as ALK rearrangement 2,5,6,7,8 1. American Society. Facts & Figures American Society. Accessed February 3, American Society. Detailed Guide: Lung (Non-Small Cell). American Society. org/acs/groups/cid/documents/webcontent/ pdf.pdf. Accessed February 3, National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Facts and Figures, American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012;

5 Learning about Lung : How ALK+ NSCLC Fits In Lung cancer is the leading cause of cancer death worldwide in both men and women 1. In the United States alone an estimated 224,210 new cases of lung cancer are estimated to be diagnosed in 2014, accounting for 13% of total cancer diagnosis 2. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85-90% of cases, and adenocarcinoma is the most common type of NSCLC % of NSCLC cases are driven by a rearrangement of the anaplastic lymphoma kinase (ALK) gene 3. which is true or false Select from the options below. GENETIC SUBTYPES Click the lungs below to learn more. More people die of lung cancer in the U.S. than of colon, breast, pancreatic and prostate cancers combined 2,4. TRUE or FALSe Not all lung cancers are the same. TRUE or FALSe The scientific community has identified 12 genetic targets that drive NSCLC 2,5,6,7,8 1. American Society. Facts & Figures American Society. Accessed February 3, American Society. Detailed Guide: Lung (Non-Small Cell). American Society. org/acs/groups/cid/documents/webcontent/ pdf.pdf. Accessed February 3, National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Facts and Figures, American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012;

6 There are Many Distinct Types of NSCLC While NSCLC used to be treated primarily based on histology, or how cancer cells look under a microscope, research in the last several years has shown that other critical factors contribute to the diagnosis and of NSCLC 1. The identification of unique genetic mutations and biomarkers that are responsible for tumor growth have changed the way we approach NSCLC, and have led to the development of personalized approaches. Approximately What % of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 2 Select from these options. WHAT GENETIC CHANGES OCCUR IN ALK+ NSCLC Click below to reveal the answer. 20% 50% 80% 100% 1. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Lin E, Li L, Guan Y, et al. Exon Array Pro ling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung s. Mol Res. 2009;7(9):

7 There are Many Distinct Types of NSCLC While NSCLC used to be treated primarily based on histology, or how cancer cells look under a microscope, research in the last several years has shown that other critical factors contribute to the diagnosis and of NSCLC 1. The identification of unique genetic mutations and biomarkers that are responsible for tumor growth have changed the way we approach NSCLC, and have led to the development of personalized approaches. Approximately What % of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 2 Select from these options. WHAT GENETIC CHANGES OCCUR IN ALK+ NSCLC Click below to reveal the answer. 20% 50% 80% 100% INCORRECT 1. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Lin E, Li L, Guan Y, et al. Exon Array Pro ling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung s. Mol Res. 2009;7(9):

8 There are Many Distinct Types of NSCLC While NSCLC used to be treated primarily based on histology, or how cancer cells look under a microscope, research in the last several years has shown that other critical factors contribute to the diagnosis and of NSCLC 1. The identification of unique genetic mutations and biomarkers that are responsible for tumor growth have changed the way we approach NSCLC, and have led to the development of personalized approaches. Approximately What % of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 2 Select from these options. WHAT GENETIC CHANGES OCCUR IN ALK+ NSCLC Click below to reveal the answer. 20% 50% 80% 100% YOU ARE CORRECT! 1. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Lin E, Li L, Guan Y, et al. Exon Array Pro ling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung s. Mol Res. 2009;7(9):

9 There are Many Distinct Types of NSCLC While NSCLC used to be treated primarily based on histology, or how cancer cells look under a microscope, research in the last several years has shown that other critical factors contribute to the diagnosis and of NSCLC 1. The identification of unique genetic mutations and biomarkers that are responsible for tumor growth have changed the way we approach NSCLC, and have led to the development of personalized approaches. Approximately What % of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 2 Select from these options. WHAT GENETIC CHANGES OCCUR IN ALK+ NSCLC Click below to reveal the answer. 20% 50% 80% 100% INCORRECT 1. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Lin E, Li L, Guan Y, et al. Exon Array Pro ling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung s. Mol Res. 2009;7(9):

10 There are Many Distinct Types of NSCLC While NSCLC used to be treated primarily based on histology, or how cancer cells look under a microscope, research in the last several years has shown that other critical factors contribute to the diagnosis and of NSCLC 1. The identification of unique genetic mutations and biomarkers that are responsible for tumor growth have changed the way we approach NSCLC, and have led to the development of personalized approaches. Approximately What % of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 2 Select from these options. WHAT GENETIC CHANGES OCCUR IN ALK+ NSCLC Click below to reveal the answer. 20% 50% 80% 100% INCORRECT 1. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Lin E, Li L, Guan Y, et al. Exon Array Pro ling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung s. Mol Res. 2009;7(9):

11 There are Many Distinct Types of NSCLC While NSCLC used to be treated primarily based on histology, or how cancer cells look under a microscope, research in the last several years has shown that other critical factors contribute to the diagnosis and of NSCLC 1. The identification of unique genetic mutations and biomarkers that are responsible for tumor growth have changed the way we approach NSCLC, and have led to the development of personalized approaches. Approximately What % of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 2 Select from these options. WHAT GENETIC CHANGES OCCUR IN ALK+ NSCLC Click below to reveal the answer. 20% 50% 80% 100% In ALK+ NSCLC, distinct portions of two genes, EML4 and ALK, can alternate and become fused together, creating an ALK fusion protein that promotes the growth of certain tumors Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Lin E, Li L, Guan Y, et al. Exon Array Pro ling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung s. Mol Res. 2009;7(9):

12 A typical patient with ALK+ NSCLC Which of these three do you feel is the most likely to be diagnosed with lung cancer PATIENT NO. 1 PATIENT NO. 2 PATIENT NO. 3 IS There A typical patient 1. Hill A, Fisher P, Yeomanson D. A s Journey: Non-small cell lung cancer. BMJ 2012;345:e Nakagawa T, Hamanaka R, Nakano T. A Case of Adolescent Lung Resectable by the Microthoracoscopic One-port Method. Tokai J Exp Clin Med. 2013;38(1): Centers for Control and Prevention. Cigarette Smoking Among Adults - United States, Morbidity and Mortality Weekly Report. Centers for Control and Prevention. Accessed February 3, Samet JM, Avila-Tang E, Rudin CM. Lung cancer in never smokers: Clinical epidemiology and environmental risk factors. Clin Res. 2009;15(18):

13 A typical patient with ALK+ NSCLC Which of these three do you feel is the most likely to be diagnosed with lung cancer PATIENT NO. 1 PATIENT NO. 2 PATIENT NO. 3 Meet Jim. Painting and photography are Jim s hobbies. A social smoker in college, Jim hasn t smoked since he graduated and moved to New York City five years ago in order to pursue his dream of becoming an artist. IS There A typical patient 1. Hill A, Fisher P, Yeomanson D. A s Journey: Non-small cell lung cancer. BMJ 2012;345:e Nakagawa T, Hamanaka R, Nakano T. A Case of Adolescent Lung Resectable by the Microthoracoscopic One-port Method. Tokai J Exp Clin Med. 2013;38(1): Centers for Control and Prevention. Cigarette Smoking Among Adults - United States, Morbidity and Mortality Weekly Report. Centers for Control and Prevention. Accessed February 3, Samet JM, Avila-Tang E, Rudin CM. Lung cancer in never smokers: Clinical epidemiology and environmental risk factors. Clin Res. 2009;15(18):

14 A typical patient with ALK+ NSCLC Which of these three do you feel is the most likely to be diagnosed with lung cancer PATIENT NO. 1 PATIENT NO. 2 PATIENT NO. 3 Meet Kathy. Like her father and brother, Kathy is a smoker. In fact, since turning 40, Kathy has been scheduling routine check-ups with her primary physician to ensure she stays in top health. IS There A typical patient 1. Hill A, Fisher P, Yeomanson D. A s Journey: Non-small cell lung cancer. BMJ 2012;345:e Nakagawa T, Hamanaka R, Nakano T. A Case of Adolescent Lung Resectable by the Microthoracoscopic One-port Method. Tokai J Exp Clin Med. 2013;38(1): Centers for Control and Prevention. Cigarette Smoking Among Adults - United States, Morbidity and Mortality Weekly Report. Centers for Control and Prevention. Accessed February 3, Samet JM, Avila-Tang E, Rudin CM. Lung cancer in never smokers: Clinical epidemiology and environmental risk factors. Clin Res. 2009;15(18):

15 A typical patient with ALK+ NSCLC Which of these three do you feel is the most likely to be diagnosed with lung cancer PATIENT NO. 1 PATIENT NO. 2 PATIENT NO. 3 Meet Gary. Gary is a non-smoker who is training for a marathon to celebrate his 50th birthday! Though arduous, Gary feels prepared given he completed a triathlon early last fall. IS There A typical patient 1. Hill A, Fisher P, Yeomanson D. A s Journey: Non-small cell lung cancer. BMJ 2012;345:e Nakagawa T, Hamanaka R, Nakano T. A Case of Adolescent Lung Resectable by the Microthoracoscopic One-port Method. Tokai J Exp Clin Med. 2013;38(1): Centers for Control and Prevention. Cigarette Smoking Among Adults - United States, Morbidity and Mortality Weekly Report. Centers for Control and Prevention. Accessed February 3, Samet JM, Avila-Tang E, Rudin CM. Lung cancer in never smokers: Clinical epidemiology and environmental risk factors. Clin Res. 2009;15(18):

16 A typical patient with ALK+ NSCLC Which of these three do you feel is the most likely to be diagnosed with lung cancer PATIENT NO. 1 PATIENT NO. 2 PATIENT NO. 3 IS There A typical patient NO Lung cancer affects a diverse group of people, including people as young as 15 1,2, and those who have never smoked or have quit several years prior to their diagnosis 2,3. In fact, 16,000 to 24,000 lung cancer deaths each year in the U.S. will be caused by factors other than active smoking 4. No one deserves this diagnosis. It s time to reduce the stigma associated with the disease. 1. Hill A, Fisher P, Yeomanson D. A s Journey: Non-small cell lung cancer. BMJ 2012;345:e Nakagawa T, Hamanaka R, Nakano T. A Case of Adolescent Lung Resectable by the Microthoracoscopic One-port Method. Tokai J Exp Clin Med. 2013;38(1): Centers for Control and Prevention. Cigarette Smoking Among Adults - United States, Morbidity and Mortality Weekly Report. Centers for Control and Prevention. Accessed February 3, Samet JM, Avila-Tang E, Rudin CM. Lung cancer in never smokers: Clinical epidemiology and environmental risk factors. Clin Res. 2009;15(18):

17 molecular in NSCLC is key can provide important information about the genetic makeup of a patient s tumor and further classify the specific type of NSCLC 1. Oncologists and pathologists are encouraged to use molecular at the time of diagnosis on all patients with advanced NSCLC to better understand which biomarkers may be driving the cancer 2. In fact, for biomarkers may 2 : > Help a physician choose the most appropriate therapy > Help to guide the selection of clinical trials for the patient s with advanced NSCLC are more likely to benefit from molecular since earlier-stage tumors are typically addressed through surgery to provide the best chance of removing the cancer 3. In 2013, three leading professional organizations* issued new evidence-based guidelines on molecular. Recommendations included 2 : Click the checkmarks to view * The College of American Pathologists (CAP), International Association for the Study of Lung (IASLC) and Association for Pathology (AMP) 1. National Human Genome Institute. Frequently Asked Questions About Genetic Testing. National Human Genome Institute. Accessed February 3, Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, 2014.

18 molecular in NSCLC is key can provide important information about the genetic makeup of a patient s tumor and further classify the specific type of NSCLC 1. Oncologists and pathologists are encouraged to use molecular at the time of diagnosis on all patients with advanced NSCLC to better understand which biomarkers may be driving the cancer 2. In fact, for biomarkers may 2 : > Help a physician choose the most appropriate therapy > Help to guide the selection of clinical trials for the patient s with advanced NSCLC are more likely to benefit from molecular since earlier-stage tumors are typically addressed through surgery to provide the best chance of removing the cancer 3. In 2013, three leading professional organizations* issued new evidence-based guidelines on molecular. Recommendations included 2 : Click the checkmarks to view Clinical characteristics such as age, gender, ethnicity and smoking history, should not be used as selection criteria for * The College of American Pathologists (CAP), International Association for the Study of Lung (IASLC) and Association for Pathology (AMP) 1. National Human Genome Institute. Frequently Asked Questions About Genetic Testing. National Human Genome Institute. Accessed February 3, Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, 2014.

19 molecular in NSCLC is key can provide important information about the genetic makeup of a patient s tumor and further classify the specific type of NSCLC 1. Oncologists and pathologists are encouraged to use molecular at the time of diagnosis on all patients with advanced NSCLC to better understand which biomarkers may be driving the cancer 2. In fact, for biomarkers may 2 : > Help a physician choose the most appropriate therapy > Help to guide the selection of clinical trials for the patient s with advanced NSCLC are more likely to benefit from molecular since earlier-stage tumors are typically addressed through surgery to provide the best chance of removing the cancer 3. In 2013, three leading professional organizations* issued new evidence-based guidelines on molecular. Recommendations included 2 : Click the checkmarks to view Clinical characteristics such as age, gender, ethnicity and smoking history, should not be used as selection criteria for s with stage four disease should be tested at time of diagnosis or at time of recurrence of progression * The College of American Pathologists (CAP), International Association for the Study of Lung (IASLC) and Association for Pathology (AMP) 1. National Human Genome Institute. Frequently Asked Questions About Genetic Testing. National Human Genome Institute. Accessed February 3, Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, 2014.

20 molecular in NSCLC is key can provide important information about the genetic makeup of a patient s tumor and further classify the specific type of NSCLC 1. Oncologists and pathologists are encouraged to use molecular at the time of diagnosis on all patients with advanced NSCLC to better understand which biomarkers may be driving the cancer 2. In fact, for biomarkers may 2 : > Help a physician choose the most appropriate therapy > Help to guide the selection of clinical trials for the patient s with advanced NSCLC are more likely to benefit from molecular since earlier-stage tumors are typically addressed through surgery to provide the best chance of removing the cancer 3. In 2013, three leading professional organizations* issued new evidence-based guidelines on molecular. Recommendations included 2 : Click the checkmarks to view Clinical characteristics such as age, gender, ethnicity and smoking history, should not be used as selection criteria for s with stage four disease should be tested at time of diagnosis or at time of recurrence of progression ALK and EGFR should be prioritized over other biomarkers * The College of American Pathologists (CAP), International Association for the Study of Lung (IASLC) and Association for Pathology (AMP) 1. National Human Genome Institute. Frequently Asked Questions About Genetic Testing. National Human Genome Institute. Accessed February 3, Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, 2014.

21 current options for NSCLC Click the options below Multiple factors are taken into account when making decisions, including type and stage of disease, whether or not biomarkers such as ALK have been identified, and the age and overall health of the patient. Nevertheless, therapies have transformed the way we approach the of NSCLC American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10:

22 current options for NSCLC Click the options below. SURGERY to remove the cancer Multiple factors are taken into account when making decisions, including type and stage of disease, whether or not biomarkers such as ALK have been identified, and the age and overall health of the patient. Nevertheless, therapies have transformed the way we approach the of NSCLC American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10:

23 current options for NSCLC Click the options below. 1 1 RADIATION to kill cancer cells 3 4 Multiple factors are taken into account when making decisions, including type and stage of disease, whether or not biomarkers such as ALK have been identified, and the age and overall health of the patient. Nevertheless, therapies have transformed the way we approach the of NSCLC American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10:

24 current options for NSCLC Click the options below. 1 2 CHEMOTHERAPY with drugs that enter the bloodstream 1 4 Multiple factors are taken into account when making decisions, including type and stage of disease, whether or not biomarkers such as ALK have been identified, and the age and overall health of the patient. Nevertheless, therapies have transformed the way we approach the of NSCLC American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10:

25 current options for NSCLC Click the options below personalized approaches based on molecular biomarkers 1 Multiple factors are taken into account when making decisions, including type and stage of disease, whether or not biomarkers such as ALK have been identified, and the age and overall health of the patient. Nevertheless, therapies have transformed the way we approach the of NSCLC American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10:

26 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

27 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. coughing 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

28 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. Dyspnea (difficult or labored breathing) 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

29 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. fatigue 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

30 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. PAIN 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

31 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. hemoptysis (spitting up blood) 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

32 Identifying in ALK+ NSCLC s first treated with an ALK inhibitor may experience disease progression, where their cancer may continue to grow or spread, less than a year after starting therapys 1. s should work closely with their healthcare team to regularly monitor for symptoms of disease progression. POSSIBLE symptoms of progression may include 2,3 : Click the options below. loss of appetite or weight loss 1. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed American Society. Detailed Guide: Lung (Non-Small Cell). American Society. documents/webcontent/ pdf.pdf. Accessed February 3, Fokas E, Steinbach JP, Rödel C. Biology of brain metastases and novel targeted therapies: time to translate the research. Biochim Biophys Acta. 2013;1835(1):61-75.

33 About Lung The Need for New ALK+ NSCLC Therapies Precision oncology has changed the diagnosis and of ALK+ NSCLC. However, more research is needed. As a leader in the forefront of oncology, Novartis is committed to ongoing research in lung cancer with the goal of developing new medicines for patients in need.

34 How Much do you know about ALK+ NSCLC Below is a review of key facts and important statistics related to ALK+ NSCLC. Click on each question mark to reveal the answer. Approximately of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 1. To date, the scientific community has identified genetic targets that drive NSCLC 4,5,6,7,8. ALK & EGFR Approximately of patients with NSCLC have the ALK gene rearrangement 3. According to leading professional organizations, genetic targets should be prioritized over other biomarkers in molecular for lung cancer % s treated with an ALK inhibitor may develop resistance and show signs of cancer progression, or that their cancer is continuing to grow or spread, after about months % Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012; Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137:

35 How Much do you know about ALK+ NSCLC Below is a review of key facts and important statistics related to ALK+ NSCLC. Click on each question mark to reveal the answer. Approximately of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 1. To date, the scientific community has identified genetic targets that drive NSCLC 4,5,6,7,8. ALK & EGFR Approximately of patients with NSCLC have the ALK gene rearrangement 3. According to leading professional organizations, genetic targets should be prioritized over other biomarkers in molecular for lung cancer % s treated with an ALK inhibitor may develop resistance and show signs of cancer progression, or that their cancer is continuing to grow or spread, after about months % Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012; Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137:

36 How Much do you know about ALK+ NSCLC Below is a review of key facts and important statistics related to ALK+ NSCLC. Click on each question mark to reveal the answer. Approximately of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 1. To date, the scientific community has identified genetic targets that drive NSCLC 4,5,6,7,8. ALK & EGFR Approximately of patients with NSCLC have the ALK gene rearrangement 3. According to leading professional organizations, genetic targets should be prioritized over other biomarkers in molecular for lung cancer % s treated with an ALK inhibitor may develop resistance and show signs of cancer progression, or that their cancer is continuing to grow or spread, after about months % Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012; Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137:

37 How Much do you know about ALK+ NSCLC Below is a review of key facts and important statistics related to ALK+ NSCLC. Click on each question mark to reveal the answer. Approximately of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 1. To date, the scientific community has identified genetic targets that drive NSCLC 4,5,6,7,8. ALK & EGFR Approximately of patients with NSCLC have the ALK gene rearrangement 3. According to leading professional organizations, genetic targets should be prioritized over other biomarkers in molecular for lung cancer % s treated with an ALK inhibitor may develop resistance and show signs of cancer progression, or that their cancer is continuing to grow or spread, after about months % Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012; Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137:

38 How Much do you know about ALK+ NSCLC Below is a review of key facts and important statistics related to ALK+ NSCLC. Click on each question mark to reveal the answer. Approximately of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 1. To date, the scientific community has identified genetic targets that drive NSCLC 4,5,6,7,8. ALK & EGFR Approximately of patients with NSCLC have the ALK gene rearrangement 3. According to leading professional organizations, genetic targets should be prioritized over other biomarkers in molecular for lung cancer % s treated with an ALK inhibitor may develop resistance and show signs of cancer progression, or that their cancer is continuing to grow or spread, after about months % Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012; Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137:

39 How Much do you know about ALK+ NSCLC Below is a review of key facts and important statistics related to ALK+ NSCLC. Click on each question mark to reveal the answer. Approximately of patients with the adenocarcinoma type of NSCLC have a genetic mutation driving their cancer 1. To date, the scientific community has identified genetic targets that drive NSCLC 4,5,6,7,8. ALK & EGFR Approximately of patients with NSCLC have the ALK gene rearrangement 3. According to leading professional organizations, genetic targets should be prioritized over other biomarkers in molecular for lung cancer % s treated with an ALK inhibitor may develop resistance and show signs of cancer progression, or that their cancer is continuing to grow or spread, after about months % Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-12. doi: /scitranslmed National Comprehensive Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung. NCCN : American Society. Detailed Guide: Lung (Non-Small Cell). American Society. Accessed February 3, Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12: Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of s With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29: Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012; Lindeman NI, Cagle PT, et al. Testing Guideline for Selection of Lung s for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: