Advances in the Treatment of
Lung Cancer
Sin Chong Lau
Consultant in Medical Oncology
41 428 new cases
13% of all new cancers
UK Cancer Incidence 2009, Cancer Research UK
41 428 new cases
13% of all new cancers
114 new cases / day
UK Cancer Mortality 2010, Cancer Research UK
34 859 deaths
22% of cancer deaths
6% of all deaths
UK Cancer Incidence 2009, Cancer Research UK
34 859 deaths
22% of cancer deaths
6% of all deaths
4 deaths / hour
UK Cancer Mortality 2010, Cancer Research UK
Survival
•
•
•
•
Men
1 year
5 years
10 years
29.4%
7.8%
4.9%
•
•
•
•
Women
1 year
5 years
10 years
33.0%
9.3%
5.9%
England 2005-09, England & Wales 2007 Survival Rates, Cancer Research UK
Survival
•
•
•
•
Men
1 year
5 years
10 years
29.4%
7.8%
4.9%
•
•
•
•
Women
1 year
5 years
10 years
33.0%
9.3%
5.9%
2nd lowest of the 21 most
common cancers
5 year survival rate
Breast cancer 85%
Colorectal cancer 55%
England 2005-09, England & Wales 2007 Survival Rates, Cancer Research UK
Progress - 5 Year Survival Rates
100
90
80
70
60
50
40
30
20
10
0
1971- 1976- 1981- 1986- 1991- 1996- 2001- 200675
80
85
90
95
00
05
09
Progress - 5 Year Survival Rates
100
90
80
70
60
50
40
30
20
10
0
1971- 1976- 1981- 1986- 1991- 1996- 2001- 200675
80
85
90
95
00
05
09
5 Year Survival Rates – By Stage
• Non-Small Cell Lung
Cancer
•
•
•
•
•
•
•
IA
IB
IIA
IIB
IIIA
IIIB
IV
58-73%
43-58%
36-46%
25-36%
19-24%
7-9%
2-13%
• Small Cell Lung Cancer
• Limited
• Extensive
18-38%
1%
Have there been any Advances in
the Treatment of Lung Cancer?
Lung Cancer
• Non-Small Cell Lung
Cancer
• 78%
• Squamous cell
carcinoma (32%)
• Adenocarcinoma (26%)
• Large cell carcinoma
• NOS (Not otherwise
specified) (35%)
• Small Cell Lung Cancer
• 18%
• Grows more rapidly
• Very closely linked to
cigarette smoking
Lung Cancer Staging
•
Non-Small Cell Lung Cancer
•
Small Cell Lung Cancer
•
Stage I – Small (<5cm) and in
only one area
•
Limited – Within one lung
field
•
Stage II – Larger, may involve
lymph nodes
•
Extensive – Outside one lung
field
•
Stage III – Larger (>7cm),
involves lymph nodes or
other parts of the chest or
lung
•
Stage IV – Spread to both
lungs, other parts of the body
or within a pleural effusion
Lung Cancer Treatment
Medical
Oncologist
Patient
Clinical
Oncologist
Surgeon
Lung
Cancer
CNS
Medical
Oncologist
Surgeon
Clinical
Oncologist
GP
Admin/
Clerical
Pathology
Clinical
Psychology
Community
Nurse
Patient
Radiotherapy
Unit
Palliative
Care
Chemotherapy
Unit
Respiratory
Physician
A&E
Radiologist
Surgical
Ward
Medical
Ward
Lung Cancer Treatment
•
•
•
Non-Small Cell Lung
Cancer
Surgery for stage I-II
Radiotherapy
•
Small Cell Lung Cancer
•
Surgery (very selected
cases)
Radiotherapy
•
– Radical for stage I-IIIA
– Palliative for stage IIIB-IV
•
– Radical for limited stage
(combined with
chemotherapy)
– Palliative or prophylactic
for extensive stage
Chemotherapy
– Adjuvant for stage I-IIIA
– Palliative for stage IIIA-IV
•
Chemotherapy
– Radical for limited stage
(combined with
radiotherapy)
– Palliative for extensive
stage
Lung Cancer Treatment - Surgery
• Non-Small Cell Lung
Cancer
• Small Cell Lung Cancer
• Not routinely practised
• Improvements in preoperative staging with
PET-CT
• Specialist lung cancer
surgeons
• Video-assisted thoracic
surgery (VATS)
lobectomy
• Adjuvant chemotherapy
PET-CT
Tumour – Benign / Malignant
Lymph nodes – Sensitive
Metastases
VATS Lobectomy
Faster recovery
Reduced post-operative pain
Lung Cancer Treatment – Adjuvant
Chemotherapy
• Non-Small Cell Lung
Cancer
• Surgically resected
• Post-operative
chemotherapy
• Treat occult
micrometastatic
disease to prevent
future cancer
recurrence
Stage
Median Overall
Survival (months)
IA – IB
48 – 59
IIA – IIB
24 – 30
IIIA -IIIB
9 - 14
SEER database validation series of over 31,000 cases
Adjuvant Chemotherapy
• IALT
– 4.3% Disease-free survival benefit at 5 years
• ANITA
– Stage II: Overall survival benefit at 5 years
improved from 39% to 52%
– Stage III: Overall survival benefit at 5 years
improved from 26% to 42%
www.adjuvantonline.com
Lung Cancer Treatment Radiotherapy
• Non-Small Cell Lung
Cancer
• Concurrent
chemoradiotherapy
• Stereotactic body
radiotherapy
• Small Cell Lung Cancer
• Prophylactic cranial
irradiation
• Concurrent
chemoradiotherapy
Concurrent Chemoradiotherapy
• Stage III non-small cell lung cancer
– Improves median overall survival by 3-4 months
(to 17 months)
– Improves 5 year survival rate from 9 to 16%
• Limited stage small cell lung cancer
– Improves 5 year survival rate from 18 to 24%
• But more side-effects
– Myelosuppression, oesophagitis, pneumonitis
RTOG 9410, JCOG 9104
Prophylactic cranial irradiation
•
Treatment of the brain with radiotherapy to prevent
recurrent cancer
•
Limited stage
– Halves (54% reduction) the risk of subsequent brain
metastases
– Improves 3 year survival rate from 15 to 21%
•
Extensive stage
– Risk of subsequent brain metastases at 1 year reduced from 40
to 15%
– Improves 1 year survival rate from 13 to 27%
•
•
Acute toxicities of fatigue, hair loss, headaches and nausea
Possible long-term risk of neurotoxicity
Stereotactic Body Radiotherapy
Standard radiotherapy – 6 weeks
5 year survival rates 10 – 30%
SBRT – 1 to 5 days
Local control rates 90%
3 year survival rates 56 – 60%
RTOG 0236
Lung Cancer Treatment Chemotherapy
•
•
•
•
Small Cell Lung Cancer
Cisplatin/Carboplatin & Etoposide
Response rates 60-90%
Median duration of response 6-8 months
OakleyOriginals
Lung Cancer Treatment Chemotherapy
• Non-small Cell Lung Cancer
• Doublet:
– Cisplatin / Carboplatin
– Etoposide / Vinorelbine / Paclitaxel / Docetaxel /
Gemcitabine / Pemetrexed
• Improves 1 year survival from 20 to 29%
• Improves quality of life
Have there been any meaningful
Advances in the Treatment of Lung
Cancer?
Targeted Therapies
Hanahan & Weinberg. Cell 100 57-70 (2000)
Imatinib
Demetri N Engl J Med 347 472-80 (2002)
Gefitinib
• 2002 – Dramatic responses (Female, East
Asian, never smokers with adenocarcinoma)
• 2004 – EGFR activating mutations predict for
response
• 2005 – ISEL trial – no benefit on unselected
patients – license withdrawn
• …..
• 2009 – IPASS trial
IPASS
• EGFR mutation positive patients
–
–
–
–
Response rate with Gefitinib 71.2%
Response rate with CbPac 47.3%
Progression free survival HR 0.48 (0.36 – 0.64)
Median overall survival >18 months (all patients)
• Driver mutations or ‘Oncogene addiction’
Other
Targets
Gene
Frequency in NSCLC
EGFR
10-35%
KRAS
15-25%
FGFR1
20%
PTEN
4-8%
ALK
3-7%
HER2
2-4%
MET
2-4%
DDR2
~4%
BRAF
1-3%
PIK3CA
1-3%
AKT1
1%
MEK1
1%
NRAS
1%
RET
1%
ROS1
1%
Crizotinib
ALK inhibitor
After 12
weeks of
treatment
Shaw N Engl J Med 365 158-67 (2011)
Other
Targets
&
Drug
Therapies
Gene
Frequency in NSCLC
Drug
EGFR
10-35%
Gefitinib, Erlotinib
KRAS
15-25%
FGFR1
20%
PTEN
4-8%
ALK
3-7%
Crizotinib
HER2
2-4%
Afatinib
MET
2-4%
Crizotinib
DDR2
~4%
Dasatininb
BRAF
1-3%
Vemurafenib
PIK3CA
1-3%
AKT1
1%
MEK1
1%
NRAS
1%
RET
1%
Sorafenib?
ROS1
1%
Crizotinib
Smoking
• 87% (men) & 84% (women) of lung cancers
attributable to smoking
• 19.4% of all new cancer cases attributable to
smoking
Smoking Cessation
Cumulative risk (%) of death from lung cancer by age 75
20
Current smoker
Stopped smoking at 60
Stopped smoking at 50
Stopped smoking at 40
Stopped smoking at 30
Lifelong non-smoker
15
10
5
0
45
50
55
60
65
70
75
Parkin Br J Cancer 105 S6-13 (2011)
Summary
• Despite advances in the treatment of lung
cancer with modern surgical and
radiotherapy techniques and novel targeted
therapies: Lung cancer survival rates are
abysmal especially when compared with
breast and bowel cancer
Summary
• Smoking cessation will prevent future
cancers and smoking rates are falling
• Personalised therapy for lung cancer is
coming
Summary
• Four more people will have
died from lung cancer in the
past hour
Thank you for listening