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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
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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
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