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Advances in the Treatment of Lung Cancer

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. UK Cancer Mortality 2010, Cancer Research UK. 114 new cases / day.

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Advances in the Treatment of Lung Cancer

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  1. Advances in the Treatment of Lung Cancer Sin Chong Lau Consultant in Medical Oncology

  2. 41 428 new cases13% of all new cancers UK Cancer Incidence 2009, Cancer Research UK

  3. 41 428 new cases13% of all new cancers UK Cancer Mortality 2010, Cancer Research UK 114 new cases / day

  4. 34 859 deaths22% of cancer deaths6% of all deaths UK Cancer Incidence 2009, Cancer Research UK

  5. 34 859 deaths22% of cancer deaths6% of all deaths UK Cancer Mortality 2010, Cancer Research UK 4 deaths / hour

  6. 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% Survival England 2005-09, England & Wales 2007 Survival Rates, Cancer Research UK

  7. 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% Survival 2ndlowest of the 21 most common cancers5 year survival rateBreast cancer 85%Colorectal cancer 55% England 2005-09, England & Wales 2007 Survival Rates, Cancer Research UK

  8. Progress - 5 Year Survival Rates

  9. Progress - 5 Year Survival Rates

  10. 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 Limited 18-38% Extensive 1% 5 Year Survival Rates – By Stage

  11. Have there been any Advances in the Treatment of Lung Cancer?

  12. 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

  13. 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 Staging

  14. Lung Cancer Treatment NONSENSE

  15. 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

  16. 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 Lung Cancer Treatment - Surgery

  17. PET-CT Tumour – Benign / Malignant Lymph nodes – Sensitive Metastases

  18. VATS Lobectomy Faster recovery Reduced post-operative pain

  19. Lung Cancer Treatment – Adjuvant Chemotherapy • Non-Small Cell Lung Cancer • Surgically resected • Post-operative chemotherapy • Treat occult micrometastatic disease to prevent future cancer recurrence SEER database validation series of over 31,000 cases

  20. 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%

  21. www.adjuvantonline.com

  22. Non-Small Cell Lung Cancer Concurrent chemoradiotherapy Stereotactic body radiotherapy Small Cell Lung Cancer Prophylactic cranial irradiation Concurrent chemoradiotherapy Lung Cancer Treatment - Radiotherapy

  23. 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

  24. 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

  25. 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

  26. Lung Cancer Treatment - Chemotherapy • Small Cell Lung Cancer • Cisplatin/Carboplatin & Etoposide • Response rates 60-90% • Median duration of response 6-8 months OakleyOriginals

  27. 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

  28. Have there been any meaningful Advances in the Treatment of Lung Cancer?

  29. Targeted Therapies Hanahan & Weinberg. Cell 100 57-70 (2000)

  30. Imatinib Demetri N Engl J Med 347 472-80 (2002)

  31. 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

  32. 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’

  33. Other Targets

  34. Crizotinib ALK inhibitor After 12 weeks of treatment Shaw N Engl J Med 365 158-67 (2011)

  35. Other Targets&DrugTherapies

  36. Smoking • 87% (men) & 84% (women) of lung cancers attributable to smoking • 19.4% of all new cancer cases attributable to smoking

  37. Smoking Cessation Parkin Br J Cancer 105 S6-13 (2011)

  38. 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

  39. Summary • Smoking cessation will prevent future cancers and smoking rates are falling • Personalised therapy for lung cancer is coming

  40. Summary • Four more people will have died from lung cancer in the past hour

  41. Thank you for listening

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