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Unmet need in squamous non-small cell lung cancer (NSCLC) Module 1 Last updated: December 2016 Contents • Epidemiology of lung cancer • Risk factors and comorbidities associated with squamous NSCLC • Treatment options for squamous NSCLC NSCLC, non-small cell lung cancer 1 Lung cancer is one of the most common cancers and is the most common cause of death by cancer worldwide1 Estimated age-standardized incidence and mortality rates (both sexes) based on 2012 data from the GLOBOCAN database1 Age-standardized rate (world) per 100,000 50 Mortality 40 30 20 10 0 Age-standardized rate (world) per 100,000 Incidence 50 40 30 20 10 • Lung cancer is the most common cause of cancerrelated death worldwide, accounting for 1.59 million deaths in 2012 (latest year for which data are available)1 • Lung cancer deaths are expected to increase more than 1.8 times over the next 20 years1 0 1. Ferlay J et al. GLOBOCAN 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx (accessed October 15, 2014) 2 Lung cancer is highly prevalent in the United States1 New cases* Rank (%) Deaths* Rank (%) Total 224,390 1st (13.3) 158,080 1st (26.5) Male 117,920 2nd (14.0) 85,920 1st (27.3) Female 106,470 2nd (12.6) 72,160 1st (25.6) *Includes estimates of both lung and bronchus cancer for 2016 5-year survival rate: 18% (patients diagnosed 2005-2011) 1. Siegel RL et al. CA Cancer J Clin 2016;66:7-30 3 Lung cancer is highly prevalent and is the most common cause of death by cancer in Europe Estimated number of new cancer cases in Europe, 2012 (excludes sex-specific cancers)a Oral cavity and pharynx Esophagus Stomach Colon and rectum Liver Gall bladder Pancreas Larynx Lung Melanoma of skin Kidney Bladder Brain, nervous system Thyroid Hodgkin's lymphoma Non-Hodgkin's… Multiple myeloma Leukemia 0 Oral cavity and pharynx Esophagus Stomach Colon and rectum Liver Gall bladder Pancreas Larynx Lung Melanoma of skin Kidney Bladder Brain, nervous system Thyroid Hodgkin's lymphoma Non-Hodgkin's… Multiple myeloma Leukemia 20 40 Age-standardized rate per 100,000 aTotal Estimated number of deaths from cancer in Europe, 2012 (excludes sex-specific cancers)a lung cancer cases: 410,000 in Europe in 2012 60 0 10 20 30 40 Age-standardized rate per 100,000 aTotal lung cancer deaths: 353,000 in Europe in 2012 1. Ferlay J et al. Eur J Cancer 2013;49:1374–403 4 Majority of patients with lung cancer are diagnosed with late-stage, locally advanced, or metastatic disease1-3 5% 16% Lung cancer SqNSCLC 22% 57% Localized Regional Distant Unstaged / Unknown Data based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program between 2005 and 20111 Disease stage at diagnosis in the United States (%) Portugal 2000–2010 (n=9767)2 Spain 1997–1999 (n=186)3 Stage IIIB/IV Early stage Disease stage at diagnosis in Europe (%) SqNSCLC, squamous non-small cell lung cancer 1. Siegel RL et al. CA Cancer J Clin 2016;66:7–30; 2. Hespanhol V et al. Rev Port Pneumol 2013;19:245–51; 3. Prim JM et al. Eur J Cancer Care 2010;19:227–33 5 Diagnoses of late-stage, locally advanced, or metastatic disease are associated with poor survival outcomes1,2 1.00 55% 50 40 30 27% 17% 20 10 Proportion still alive 5-year relative survival, % 60 0.75 0.50 Stage I Stage II Stage III Stage IV All NSCLC All lung cancer 0.25 4% 0 Localized Regional Distant All stages The standard error of the survival rate is between 5 and 10 percentage points. Data based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program between 2005 and 20111 0 0 100 200 300 Days 400 500 Survival study data from patients with lung cancer in England and Wales. The median survival for patients was 293 days for stage III disease and 100 days for stage IV in 20132 Re-used with permission of the Health and Social Care Information Centre, also known as NHS Digital. All rights reserved NSCLC, non-small cell lung cancer 1. Siegel RL et al. CA Cancer J Clin 2016;66:7–30; 2. HSCIC. National Lung Cancer Audit: 2013 Patient Cohort. Available at: http://www.hscic.gov.uk/catalogue/PUB16019 (accessed June 27, 2016) 6 Incidence of lung cancer per 100,000 people / years (95% CI)1 Incidence and early death of lung cancer are associated with socioeconomic deprivation in the UK 80 60 40 20 0 1 (affluent) 2 3 4 5 (deprived) 4 n=269 5 (deprived) n=224 OR (95% CI) for death within 90 days of diagnosis2 p=0.017 1.30 1.20 1.10 1.00 0.90 0.80 1 (affluent) n=165 2 n=190 3 n=201 Townsend Deprivation Index Quintile 1Data taken from a UK database (THIN), a computerised, longitudinal, primary care dataset with cases extracted from January 2000–January 2009 2Multivariate analysis using data taken from a UK database (THIN), with cases extracted from January 200–January 2013 CI, confidence interval; OR, odds ratio; THIN, The Health Improvement Network 1. Iyen-Omofoman B et al. BMC Public Health 2011;11:857; 2. O’Dowd EL et al. Thorax 2015;70:161–8 7 Age-standardized incidence rate of lung cancer per 100,000 people / years (95% CI)1 Incidence and survival after lung cancer are associated with socioeconomic deprivation in North America and Europe 140 120 100 80 60 40 20 0 1 (deprived) 2 3 4 5 (affluent) Income quintile 1.2 HR (95% CI) for overall death2 1.0 0.8 0.6 0.4 0.2 0.0 High Medium Low Income level 1Prospective analysis using data taken from the Canadian Census Cohort, with cases extracted from 1991 to 2003 2Multivariate logistic regression analysis using data taken from the Danish Lung Cancer Register, with cases extracted from 2004 to 2010 CI, confidence interval; HR, hazard ratio 1. Mitra D et al. Health Rep 2015;26:12–20; 2. Dalton SO et al. Acta Oncol 2015;54:797–804 8 Epidemiology of NSCLC • NSCLC represents ~85% of all cases of lung cancer1 Prevalence of NSCLC subtypes1 20–30% Squamous Other (adenocarcinoma, large cell carcinoma, NSCLC nos) 70–80% Data based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program between 2004 and 20091 • Globally, squamous NSCLC accounts for 27–46% of NSCLC cases in men and 11–28% of cases in women2 NSCLC, non-small cell lung cancer; nos, not otherwise specified 1. Houston KA et al. Lung Cancer 2014;86:22–8; 2. Youlden DR et al. J Thorac Oncol 2008;3:819–31 9 Adenocarcinoma vs squamous cell carcinoma in NSCLC: pathology Adenocarcinoma1,2,4 Squamous1-4 H-E stain X150 H-E stain X150 Images used with permission of the Radiological Society of North America • • • Presence of glands and papillary structures (*) Neoplastic cells with round to oval nuclei, prominent nucleoli, and moderate amounts of cytoplasm Positive for mucin, TTF-1, cytokeratin 7 • • • • • Flattened appearance (i.e., “squamous”) Intercellular bridges Individual cell keratinization (arrowhead) Keratin pearls Positive for p63, p40, cytokeratin 5/6 NSCLC, non-small cell lung cancer; TTF-1, thyroid transcription factor 1 1. Rosado-de-Christenson ML et al. Radiographics 1994;14:429–46; 2. Oliver TG et al. Am J Clin Oncol 2015;38:220–6; 3. Bishop JA et al. Mod Pathol 2012;25:405–15; 4. Travis WD et al. J Thorac Oncol 2015;10:1243–60 10 Key differences between adenocarcinoma and squamous NSCLC Parameter Adenocarcinoma Squamous cell carcinoma Patient demographics Over twice as common as any other lung cancer histology in women; most common histology in nonsmokers; patients tend to be younger1-4 More prevalent in men; stronger association with smoking; patients tend to be slightly older1-4 Tumor location Peripheral5,6 Central (higher incidence of hemorrhages from blood vessel invasion and bronchial obstruction)5-7 Cavitation Not typical5,6 Typical5,6 Disease stage at presentation Metastatic disease often presents before symptom development8 More likely to be detected at localized stage due to earlier onset of symptoms8 Metastasis Brain metastases are more common9 Brain metastases are less common9 NSCLC, non-small cell lung cancer 1. Cetin K et al. Clin Epidemiol 2011;3:139–48; 2. Pesch B et al. Int J Cancer 2012;131:1210–9; 3. Radzikowska E et al. Ann Oncol 2002;13:1087–93; 4. Houston KA et al. Lung Cancer 2014;86:22–8; 5. Rosado-de-Christenson ML et al. Radiographics 1994;14:429–46; 6. Nichols L et al. Arch Pathol Lab Med 2012;136:1552–7; 7. Ito M et al. BMC Cancer 2012;12:27; 8. Hirsch FR et al. J Thorac Oncol 2008;3:1468–81; 9. Mujoomdar A et al. Radiology 2007;242:882–8 11 Advanced squamous NSCLC is an aggressive cancer associated with a worse prognosis than nonsquamous NSCLC, irrespective of treatment1-6 Based on recent clinical trials, median OS in patients with advanced squamous NSCLC following 1st-line therapy is 9–11 months4,6 compared with 12–14 months for those with advanced nonsquamous* disease3-6 Median OS, months • 14 12 10 8 6 4 2 0 ~30% Squamous Nonsquamous* Data based on Phase III clinical trials of different 1st-line interventions in advanced NSCLC3-6 The shaded portion of each bar represents the range *There are 4 main pathological types of lung cancer (adeno-, squamous cell, small cell and large cell carcinoma). For reasons of clinical consequences, different pathological types of lung cancer are sometimes grouped into a category (non-small cell carcinoma or nonsquamous non-small cell carcinoma) when it is necessary or useful to consider them in the same way, even if the tumors are pathologically different NSCLC, non-small cell lung cancer; OS, overall survival 1. Wilson DO et al. Am J Respir Crit Care Med 2012;185:85–9; 2. Veronesi G et al. Ann Intern Med 2012;157:776–84; 3. Sandler A et al. N Engl J Med 2006;355:2542–50; 4. Socinski MA et al. J Clin Oncol 2012;30:2055–62; 5. Paz-Ares LG et al. J Clin Oncol 2013;31:2895–902; 6. Scagliotti GV et al. J Clin Oncol 2008;26:3543–51 12 The location of squamous NSCLC tumors makes them challenging to treat1,2 • Squamous NSCLC is typically centrally located close to blood vessels1 and may be more likely to invade larger blood vessels, potentially resulting in fatal hemorrhages2 • Peripherally located squamous NSCLC usually presents when the tumor is larger and has invaded the chest wall3 Squamous cell carcinoma NSCLC, non-small cell lung cancer 1. Rosado-de-Christenson ML et al. Radiographics 1994;14:429–46; 2. Nichols L et al. Arch Pathol Lab Med 2012;136:1552–7; 3. Rubin E, Reisner HM (eds). Essentials of Rubin’s Pathology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009 13 Smoking has a stronger association with squamous NSCLC than other NSCLC and impacts on outcome1-4 • Tobacco consumption is peaking in non-western countries where the incidence of lung cancer is expected to rise1 • Active tobacco smoking has a stronger association with squamous NSCLC than with other NSCLC2,3 • In a pooled analysis of >13,000 case-control studies, the OR for squamous disease in current vs never smokers was 45.6 vs10.8 for adenocarcinoma3 • Mortality rates for patients with squamous NSCLC who have ever smoked are twice those for adenocarcinoma4 • Indirect estimates are based on a systematic review of 148 studies4 NSCLC, non-small cell lung cancer; OR, odds ratio 1. Torre LA et al. CA Cancer J Clin 2015;65:87–108; 2. Khuder A. Lung Cancer 2001;31:139–48; 3. Pesch B et al. Int J Cancer 2012;131:1210–9; 4. Lee PN, Forey BA. BMC Cancer 2013;13:189 14 Role of age and comorbidity in NSCLC1,2 • Both squamous and adenocarcinoma NSCLC are associated with increased age1 • Serious comorbidities (i.e., cardiovascular disease and COPD) are more prevalent in lung cancer patients aged ≥70 years2 • In patients aged ≥70 years, those with squamous NSCLC have a higher incidence of comorbidity compared with adenocarcinoma, large-cell undifferentiated carcinoma, and small-cell carcinoma2 Prevalence of serious comorbidities in NSCLC patients, % Patients aged ≥65 years at NSCLC diagnosis, % 80 60 40 20 0 Squamous NSCLC Adenocarcinoma Data taken from 51,749 patients diagnosed in the US between 1998 and 2003 as part of the NCI’s SEER program1 80 60 40 20 0 <70 years ≥70 years Data based on a population-based registry of 3864 patients with lung cancer2 COPD, chronic obstructive pulmonary disease; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; SEER, Surveillance, Epidemiology, and End Results 1. Cetin K et al. Clin Epidemiol 2011;3:139–48; 2. Janssen-Heijnen ML et al. Lung Cancer 1998;21:105–13 15 Squamous NSCLC is associated with challenging comorbidities that make treatment of the disease more difficult1-4 • Many patients with squamous NSCLC have age- and smoking-related comorbidities at the time of diagnosis1-3 • Patients with squamous NSCLC have a 64% incidence of comorbid disease at diagnosis vs 52% for those with other lung cancers1 • Comorbid conditions increase the difficulty of treating patients • The presence of comorbidities has been associated with poorer survival2,3 • In a NSCLC study, patients with severe comorbidities had a higher incidence of specific grade 3 / 4 adverse events following chemotherapy4 Patients with severe comorbidities Patients with no severe comorbidities p value Neutropenic fevers 12% 5% 0.01 Death from neutropenic fever 3% 0% 0.03 Thrombocytopenia 46% 36% 0.03 Adverse event (grade 3 / 4) NSCLC, non-small cell lung cancer 1. Janssen-Heijnen ML et al. Lung Cancer 1998;21:105–13; 2. Asmis TR et al. J Clin Oncol 2008;26:54–9; 3. Putila J, Guo NL PLoS One 2014;9:e100994; 4. Grønberg BH et al. Eur J Cancer 2010;46:2225–34 16 In addition to lung cancer, smoking is associated with many other diseases1 • Smoking is formally established as a causative link to 21 diseases, including COPD and CVD,1 but in addition, pooled data from 5 cohort studies (n=954,029 patients aged ≥55 years) has now highlighted excess mortality from causes not previously recognized as being associated with smoking Disease RR (95% CI) for mortality Renal failure 2.0 (1.7, 2.3) Hypertensive heart disease 2.4 (1.9, 3.0) Intestinal ischemia 6.0 (4.5, 8.1) Infections 2.3 (2.0, 2.7) Other respiratory disordersa 2.0 (1.6, 2.4) Prostate cancer 1.4 (1.2, 1.7) Breast cancer 1.3 (1.2, 1.5) Liver cirrhosis 3.1 (2.6, 3.7) aExcludes pneumonia, influenza, COPD, and pulmonary fibrosis • The additional potential disease burden due to smoking further increases the challenge of managing squamous NSCLC CI, confidence interval; COPD, chronic obstructive pulmonary disorder; CVD, cardiovascular disease; NSCLC, non-small cell lung cancer 1. Carter BD et al. N Engl J Med 2015;372:631–40 17 Nearly 50% of patients have a performance status of 2–4 at diagnosis • In a recent survey of patients diagnosed in 2013 in the UK, 19.6% had a PS of 2, 18% had a PS of 3, and 6.4% had a PS of 4 PS of patients in England and Walesa in 2013, % (n>30,000) PS 0 PS 1 PS 2 PS 3 PS 4 • Patients may not receive a full diagnostic evaluation due to poor PS or cancer staging aData were collected from various strategic clinical networks throughout England and Wales for patients first diagnosed with lung cancer PS, performance status HSCIC. National Lung Cancer Audit: 2013 Patient Cohort. Available at: http://www.hscic.gov.uk/catalogue/PUB16019 (accessed June 27, 2016) 18 Improvements in survival over recent decades have been greater in stage IV adenocarcinoma vs squamous NSCLC1 Stage IV NSCLC 1-year survival: adenocarcinoma vs squamous1 % patients 20 * 25 Adenocarcinoma 1-year survival Squamous 1-year survival 20 % patients 25 Stage IV NSCLC 2-year survival: adenocarcinoma vs squamous1 15 10 5 Adenocarcinoma 2-year survival Squamous 2-year survival 15 10 5 0 0 1990–1993 1994–1997 1998–2001 Time period of diagnosis 2002–2005 1990–1993 1994–1997 1998–2001 Time period of diagnosis 2002–2005 Based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program for patients diagnosed between 1990 and 2005 with stage IV NSCLC1; *p=0.02 • Survival has been improving since 1990 for NSCLC of all histologies1 • Survival significantly increased for patients diagnosed in 2002–2005 with adenocarcinoma compared with those diagnosed with squamous NSCLC1 NSCLC, non-small cell lung cancer 1. Morgensztern D et al. J Thorac Oncol 2009;4:1524–9 19 In contrast to nonsquamous* NSCLC, survival in advanced squamous NSCLC has remained relatively unchanged for more than 2 decades1-10 Examples of OS from start of 1st-line therapy in advanced NSCLC patients Median OS, months NSCLC (all histologies) 18 16 14 12 10 8 6 4 2 0 Single-agent platinum 1980s1,2 Platinumbased doublets 1990–20053-5 Squamous Platinumbased doublets Nonsquamous Histologydirected therapy Platinum-triplet therapy (BEV) New strategies Platinumbased doublets 2005–20096-8 2010–20159,10 Pemetrexed and bevacizumab are contraindicated in SqCLC histology; there are no oncogene-directed targeted therapy in squamous histology to date *There are 4 main pathological types of lung cancer (adeno-, squamous cell, small cell and large cell carcinoma). For reasons of clinical consequences, different pathological types of lung cancer are sometimes grouped into a category (non-small cell carcinoma or nonsquamous non-small cell carcinoma) when it is necessary or useful to consider them in the same way, even if the tumors are pathologically different Very few new 1st-line treatment options have been approved for patients with squamous NSCLC11 BEV, bevacizumab; NSCLC, non-small cell lung cancer; OS, overall survival; Pem, pemetrexed. 1. Bonomi PD et al. J Clin Oncol 1989;7:1602–13; 2. Eagan RT et al. J Clin Oncol 1988;6:5–8; 3. Schiller JH et al. N Engl J Med 2002;346:92–8; 4. Sandler AB et al. J Clin Oncol 2000;18:122–30; 5. Spira A, Ettinger DS. N Engl J Med 2004;350:379–92; 6. Sandler A et al. N Engl J Med 2006;355:2542–50; 7. Scagliotti GV et al. J Clin Oncol 2008;26:3543–51; 8. Scagliotti G et al. Oncologist 2009;14:253–63; 9. Socinski MA et al. J Clin Oncol. 2012;30:2055–62; 10. Paz-Ares LG et al. J Clin Oncol. 2013;31:2895–902; 11. Socinski MA et al. J Thorac Oncol 2016;11:1411–22 20 Treatment in advanced NSCLC is driven by histological subtype, performance status, and oncogenic testing according to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)1 Histological subtype Oncogenic testing 1st line EGFR-mutation positive Erlotinib or afatinib or gefitinib (all category 1) ALK-mutation positive Crizotinib (category 1) PS 0–1: doublet chemotherapy (category 1) or PT-doublet + bevacizumab Adenocarcinoma, large cell, NSCLC NOS EGFR- / ALK-mutation negative PS 2: chemotherapy Stable disease / overall response: continuation or switch maintenance or close observation Squamous Testing should be considered in patients who have never been smokers, have a small biopsy specimen, or have mixed histology PS 0–1: doublet chemotherapy (category 1) PS 2: chemotherapy Stable disease / overall response: continuation or switch maintenance or close observation Necitumumab + gemcitabine-cisplatin is FDA / EMA approved for metastatic SqCLC.2,3 The NCCN does not include necitumumab + gemcitabine-cisplatin as a treatment option1 ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; NOS, not otherwise specified; PS, performance status; PT, platinum based; SqCLC, squamous cell lung cancer; TKI, tyrosine kinase inhibitor 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2017. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed February 21, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way; 2. FDA. Necitumumab. Highlights of prescribing information. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125547s000lbl.pdf (accessed June 20, 2016); 3. EMA. Necitumumab summary of product characteristics. 2016. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003886/WC500202694.pdf (accessed June 20, 2016). 21 Currently approved therapies in NSCLC often have reduced efficacy or greater toxicity in squamous vs nonsquamous1-8 • Distinctions between adenocarcinoma and squamous NSCLC are becoming increasingly important in predicting therapeutic response and toxicity1,2 • The efficacy of systemic therapies in nonsquamous* NSCLC is often reduced in squamous NSCLC • A 1st-line chemotherapy doublet increased survival in patients with nonsquamous* NSCLC vs an established chemotherapy combination but failed to do so in patients with squamous NSCLC3 • EGFR and ALK TKIs are effective in mutation-positive NSCLC4-6; however, these mutations are extremely rare in squamous NSCLC6,7 • Squamous histology is also a predictor of poor local control8 *There are 4 main pathological types of lung cancer (adeno-, squamous cell, small cell and large cell carcinoma). For reasons of clinical consequences, different pathological types of lung cancer are sometimes grouped into a category (non-small cell carcinoma or nonsquamous non-small cell carcinoma) when it is necessary or useful to consider them in the same way, even if the tumors are pathologically different ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor 1. Zugazagoitia J et al. J Thorac Dis 2014;6(Suppl 5):S526–36; 2. Perez-Moreno P et al. Clin Cancer Res 2012;18:2443–51; 3. Scagliotti GV et al. J Clin Oncol 2008;26:3543–51; 4. Mok T et al. N Engl J Med 2009;361:947–57; 5. Kwak E et al. N Engl J Med 2010;363:1693–703; 6. Pao W et al. Proc Natl Acad Sci USA 2004;101:13306–11; 7. Liao RG et al. Lung Cancer Manag 2012;1:293–300; 8. McAvoy S et al. Int J Radiat Oncol Biol Phys 2014;90:819–27 22 Fewer patients with stage IV squamous NSCLC receive chemotherapy (1 of 2) • In a large study conducted in the Netherlands, fewer patients with stage IV squamous NSCLC received chemotherapy compared with those with stage IV adenocarcionoma1 Chemotherapy use in stage IV NSCLC in the Southern Netherlands, 2001–20121 Histology n Chemotherapy, % of patients Squamous 985 38 2,112 52 Adenocarcinoma • In addition to adenocarcinoma diagnosis, factors associated with treatment were younger age, higher socioeconomic status, no comorbidities, and recent diagnosis1 • Patients who received chemotherapy had improved survival: • For those aged 65–74 years, 64% survived at 6 months with chemotherapy, compared with only 19% without chemotherapy1 NSCLC, non-small cell lung cancer 1. Aarts MJ et al. Int J Cancer 2015;136:E387–95 23 Fewer patients with stage IV squamous NSCLC receive chemotherapy1 (2 of 2) • In a study of 8113 Canadian patients with stage IV NSCLC, most patients did not receive systemic therapy1 • • Patients with squamous NSCLC and older patients were less likely to receive chemotherapy The use of systemic therapy for treatment of patients increased from 19% in 2005 to 26% in 2009 (p<0.0001) 1st-line chemotherapy received No chemotherapy received 24% 76% 2nd-line chemotherapy received No 2nd-line chemotherapy received 31% 69% Data for treatment utilization was based on 8113 Canadian patients who were identified as having stage IV NSCLC between 2005 and 20091 NSCLC, non-small cell lung cancer 1. Sacher AD et al. Cancer 2015;121:2562–9 24 Oncogenic drivers with effective treatments are rare in squamous NSCLC vs adenocarcinoma1-3 Adenocarcinoma1 EGFR M+ 15–20% Unknown oncogenic drivers or oncogenic drivers without proven treatments Squamous NSCLC2,3 EGFR M+ or EML4-ALK+ <5% EML4-ALK+ 3–7% Unknown oncogenic drivers or oncogenic drivers without proven treatments ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer 1. Gerber DE et al. Am Soc Clin Oncol Educ Book 2014:e353–65; 2. Pao W, Girard N. Lancet Oncol 2011;12:175–80; 3. Perez-Moreno P et al. Clin Cancer Res 2012;18:2443–51 25 Research into 1st-line treatments for squamous NSCLC has proved extremely challenging1-7 • Treatments that target numerous pathways have failed in clinical trials in squamous NSCLC patients: • • • • • Antiangiogenics1 Multikinase inhibitors2,3 Protein modifiers4 IGF-1R mAb5 EGFR mAb6-9 • Reasons for failure in clinical trials can include: failure to meet primary endpoint, unacceptable toxicity, and unfavorable risk:benefit ratio • Trial design, chemotherapy backbone, and the patient population can also contribute to trial failure EGFR, epidermal growth factor receptor; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer 1. Johnson DH et al. J Clin Oncol 2004;22:2184–91; 2. Scagliotti GV et al. J Clin Oncol 2012;30:2829–36; 3. Scagliotti G et al. J Clin Oncol 2010;28:1835–42; 4. Sanofi. Press release, June 3, 2013. Available at: http://en.sanofi.com/Images/33127_20130603_rdupdate_en.pdf. Accessed October 15, 2014; 5. Langer CJ et al. J Clin Oncol 2014;32:2059–66; 6. Pirker R et al. Lancet 2009;373:1525–31; 7. European Medicines Agency. Assessment Report for Erbitux. London, UK: 2010; 8. Pirker R et al. Lancet Oncol 2012;13:33–42; 9. European Medicines Agency. Withdrawal Assessment Report for Erbitux. London, UK: 2012 26 Radiation therapy can provide palliation of thoracic symptoms irrespective of systemic therapy • Substantial evidence supports the efficacy of external beam radiotherapy (RT), either alone or in combination with concurrent chemotherapy, in the palliation of thoracic symptoms such as hemoptysis, cough, chest pain, and airway obstruction1,2 • • RT may be the primary or only option for patients with poor performance status and advanced disease and for those who have declined or progressed despite systemic therapy In patients with advanced disease, palliative thoracic RT ≥35 Gy10 significantly improved total symptom score and survival compared with lower doses2 • Patients should be informed of the potential disadvantages of high-dose RT (higher incidence of esophagitis and greater time investment) • Patients with short expected survival can be treated with short-course palliative RT with minimal toxicity and inconvenience 1. Rodrigues G et al. Pract Radiat Oncol 2011;1:60–71; 2. Fairchild A et al. J Clin Oncol 2008;26:4001–11 27 Conclusions • Squamous NSCLC is an aggressive and difficult-to-treat form of NSCLC, with 30% lower OS than nonsquamous* NSCLC • Advancing age and smoking are the predominant risk factors in squamous NSCLC, and the comorbidities associated with these factors make the disease challenging to treat • Treatment in advanced NSCLC is driven by histological subtype and oncogenic testing • There are fewer treatment options for squamous compared with nonsquamous* NSCLC Platinum-based chemotherapy has been the only 1st-line treatment option for most patients with squamous NSCLC for the last 2 decades, reflecting a significant unmet need for treatment advances in this patient population *There are 4 main pathological types of lung cancer (adeno-, squamous cell, small cell and large cell carcinoma). For reasons of clinical consequences, different pathological types of lung cancer are sometimes grouped into a category (non-small cell carcinoma or nonsquamous non-small cell carcinoma) when it is necessary or useful to consider them in the same way, even if the tumors are pathologically different NSCLC, non-small cell lung cancer; OS, overall survival 28