advances in the treatment of lung cancer sin chong lau consultant in medical oncology
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Advances in the Treatment of Lung Cancer
Sin Chong Lau
Consultant in Medical Oncology
41 428 new cases13% of all new cancers
UK Cancer Incidence 2009, Cancer Research UK
41 428 new cases13% of all new cancers
UK Cancer Mortality 2010, Cancer Research UK
114 new cases / day
34 859 deaths22% of cancer deaths
6% of all deaths
UK Cancer Incidence 2009, Cancer Research UK
34 859 deaths22% of cancer deaths
6% of all deaths
UK Cancer Mortality 2010, Cancer Research UK
4 deaths / hour
Survival
• Men• 1 year 29.4%• 5 years 7.8%• 10 years 4.9%
• Women• 1 year 33.0%• 5 years 9.3%• 10 years 5.9%
England 2005-09, England & Wales 2007 Survival Rates, Cancer Research UK
Survival
• Men• 1 year 29.4%• 5 years 7.8%• 10 years 4.9%
• Women• 1 year 33.0%• 5 years 9.3%• 10 years 5.9%
England 2005-09, England & Wales 2007 Survival Rates, Cancer Research UK
2nd lowest of the 21 most common cancers
5 year survival rateBreast cancer 85%Colorectal cancer 55%
Progress - 5 Year Survival Rates
0102030405060708090
100
1971-75
1976-80
1981-85
1986-90
1991-95
1996-00
2001-05
2006-09
Progress - 5 Year Survival Rates
0102030405060708090
100
1971-75
1976-80
1981-85
1986-90
1991-95
1996-00
2001-05
2006-09
5 Year Survival Rates – By Stage
• Non-Small Cell Lung Cancer
• IA 58-73%• IB 43-58%• IIA 36-46%• IIB 25-36%• IIIA 19-24%• IIIB 7-9%• IV 2-13%
• Small Cell Lung Cancer
• Limited18-38%• Extensive 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
• Stage I – Small (<5cm) and in only one area
• Stage II – Larger, may involve lymph nodes
• 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
• Small Cell Lung Cancer
• Limited – Within one lung field
• Extensive – Outside one lung field
Lung Cancer Treatment
ClinicalOncologist
Surgeon
MedicalOncologist
Patient
NONSENSE
LungCancerCNS
GP
Pathology
ClinicalPsychology
PalliativeCare
RespiratoryPhysician
Radiologist
SurgicalWard
MedicalWard
A&E
Chemo-therapyUnit
Radio-therapyUnit
CommunityNurse
Admin/Clerical
ClinicalOncologist
Surgeon
MedicalOncologist
Patient
Lung Cancer Treatment
• Non-Small Cell Lung Cancer
• Surgery for stage I-II• Radiotherapy
– Radical for stage I-IIIA– Palliative for stage IIIB-IV
• Chemotherapy– Adjuvant for stage I-IIIA– Palliative for stage IIIA-IV
• Small Cell Lung Cancer
• Surgery (very selected cases)
• Radiotherapy– Radical for limited stage
(combined with chemotherapy)
– Palliative or prophylactic for extensive stage
• Chemotherapy– Radical for limited stage
(combined with radiotherapy)
– Palliative for extensive stage
Lung Cancer Treatment - Surgery
• Non-Small Cell Lung Cancer
• Improvements in pre-operative staging with PET-CT
• Specialist lung cancer surgeons
• Video-assisted thoracic surgery (VATS) lobectomy
• Adjuvant chemotherapy
• Small Cell Lung Cancer
• Not routinely practised
PET-CT
Tumour – Benign / Malignant
Lymph nodes – Sensitive
Metastases
Faster recovery
Reduced post-operative pain
VATS Lobectomy
Lung Cancer Treatment – Adjuvant Chemotherapy• Non-Small Cell Lung
Cancer• Surgically resected
• Post-operative chemotherapy
• Treat occult micrometastatic disease to prevent future cancer recurrence
StageMedian 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%
Shaw N Engl J Med 365 158-67 (2011)
Crizotinib
ALK inhibitor
After 12 weeks of treatment
Other Targets&DrugTherapies
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
0
5
10
15
20
45 50 55 60 65 70 75
Current smoker
Stopped smoking at 60
Stopped smoking at 50
Stopped smoking at 40
Stopped smoking at 30
Lifelong non-smoker
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