1. Jacob Sands, MD Dana-Farber Cancer Institute October 25, 2017
Lung Cancer Updates
Jacob Sands, MD
Dana-Farber Cancer Institute
October 25, 2017

2. Advances in Lung Cancer
Epidemiology
Targeted Therapy
Immunotherapy
Lung Screening

3. Advances in Lung Cancer
Epidemiology
Targeted Therapy
Immunotherapy
Lung Screening

4. Advances in Lung Cancer
Epidemiology
Targeted Therapy
Immunotherapy
Lung Screening

5. Epidemiology
Trends in Death Rates Among Males for Selected Cancers, United States, 1930 to Rates are age adjusted to the 2000 US standard population. Due to changes in International Classification of Diseases (ICD) coding, numerator information has changed over time. Rates for cancers of the lung and bronchus, colorectum, and liver are affected by these changes. (Reprinted with permission from John Wiley and Sons [Siegel R, Naishadham D, Jemal A. Cancer Statistics, 2012.CA Cancer J Clin 2012; 62:10–29]; copyright 2012 American Cancer Society, Inc.)

6. Overall Survival NSCLC
Clinical Stage
Pathologic Stage
MST= Median Survival Time
Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2:706.

7. Advances in Lung Cancer
Epidemiology
Targeted Therapy
Immunotherapy
Lung Screening

8. EGFR Mutations (the beginning)

10. EGFR mutation
First line treatment with EGFR-TKI was established including gefitinib and erlotinib.
Erlotinib – US
Gefitinib – Asia and Europe

11. EGFR mutation
First line treatment with EGFR-TKI was established including gefitinib and erlotinib.
Erlotinib – US
Gefitinib – Asia and Europe
Then
Afatinib (Lux Lung 3 published 2013 but first line 2016)
Osimertinib (T790M, published 2/16/2017)
Dacomitinib (presented June, 2017 but not FDA approved therapy)

12. Newest EGFR FLAURA Median PFS (HR 0.46, p<0.001)
Osimertinib 18.2 mos
Gefinitib/Erlotinib 10.2 mos
Overall Survival not yet mature but trending promising
Improved outcomes in brain mets
Progression in the brain:
6% osimertinib
15% gefitinib/erlotinib

13. Newest EGFR FLAURA 54% improvement in PFS with osimertinib
Duration of response significantly higher
Improved outcomes in brain
Grade 3/4 events about 12% lower in the osimertinib arm

14. ALK Crizotinib has been standard of care 1st line (published 2013)
Ceritinib
Lorlatinib
Brigatinib
Alectinib

15. ALK Alectinib

16. ALK Alectinib

17. BRAF V600E

18. BRAF V600E (dabrafenib plus trametinib)

19. Small Cell Lung Cancer
No established targeted therapy

20. Small Cell Lung Cancer DLL-3 is a potential target
AbbVie paid $5.8 billion upfront with $4 billion reserved for milestones to purchase Rova-T from Stemcentrx

21. Small Cell Lung Cancer, rovalpituzumab

22. Advances in Lung Cancer
Epidemiology
Targeted Therapy
Immunotherapy
Lung Screening

23. Immunotherapy
Nivolumab
Pembrolizumab
Atezolizumab
Durvalumab

24. Immunotherapy
Nivolumab
Pembrolizumab
Atezolizumab
Durvalumab

25. Immunotherapy
Nivolumab
Pembrolizumab
Atezolizumab
Durvalumab

26. Immunotherapy
Nivolumab
Pembrolizumab
Atezolizumab
Durvalumab

27. Non-Small Cell Lung Cancer
Squamous
Non-Squamous

28. Pacific (durvalumab after chemo/rads for stage 3)

29. Advances in Lung Cancer
Epidemiology
Targeted Therapy
Immunotherapy
Lung Screening

30. Trends in Death Rates Among Males for Selected Cancers, United States, 1930 to Rates are age adjusted to the 2000 US standard population. Due to changes in International Classification of Diseases (ICD) coding, numerator information has changed over time. Rates for cancers of the lung and bronchus, colorectum, and liver are affected by these changes. (Reprinted with permission from John Wiley and Sons [Siegel R, Naishadham D, Jemal A. Cancer Statistics, 2012.CA Cancer J Clin 2012; 62:10–29]; copyright 2012 American Cancer Society, Inc.)

31. Overall Survival NSCLC
Clinical Stage
Pathologic Stage
MST= Median Survival Time
Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2:706.

32. Non-Small Cell Lung Cancer
Many patients become symptomatic with clinical stage IV disease

33. Non-Small Cell Lung Cancer
Many patients become symptomatic with clinical stage IV disease
5 year survival = 2%

34. Non-Small Cell Lung Cancer
Clinical stage IA
5 year overall survival = 50%
Pathologic stage IA
5 year overall survival = 73%
Early stage lung cancer screening
5 year overall survival about 90%

35. Non-Small Cell Lung Cancer
About 63-70% of patients diagnosed in screened population have stage I lung cancer
Early stage lung cancer screening
5 year overall survival about 90%

36. Lung Cancer Screening

37. National Lung Screening Trial
Multi-center randomized controlled trial
Low dose non-contrast CT scan
Single view posteroanterior chest radiography
Total of 53,454 persons were enrolled
Study cost: $250 million

38. NLST: Lung Cancer Diagnoses

39. NLST: Death from Lung Cancer

40. NLST
The 892 lung cancers in participants with no screening test included 35 in participants who were never screened, 802 that were diagnosed during the post-screening period, and 55 in
participants who were due for a screening test.

41. NLST
The 892 lung cancers in participants with no screening test included 35 in participants who were never screened, 802 that were diagnosed during the post-screening period, and 55 in participants who were due for a screening test.

43. National Concerns/Criticisms
Increased radiation exposure
“False positives”
We are invasively treating indolent cancers
Cost to the system

44. Average age of patients in screening trials is 62
Radiation Exposure
LDCT
1 mSv
Years of annual lung screening
Mammogram
.7 mSv
Lumbar Spine Films
2 mSv 2
Diagnostic Chest CT
10 mSv 10
Triphasic CT AB/P
25 mSv 25
Background Exposure Colorado
3 mSv/year
11.8 mSv/year 3
11.8
Occupational Exposure
50 mSv/year 50
Transatlantic Flight
.1 mSv
10 flights = 1 LDCT
Here is a chart for comparison purposes. LDCT exposure is similar to a mammogram. A Lumbar spine film series is 2mSv or the equivalent of 2 years of annual LDCT scanning. Triphasic CT abd/pel is 25mSv. Background exposure is 3 mSv at sea level and 11.8mSv in Denver Colorado. Occupational exposure for a radiation worker is 50mSv, which is the equivalent of 50 LDCT studies. A transatlantic flight is .1mSv such that 7 transatlantic flights equals 1 LDCT. Also an important consideration regarding radiation risk is the year latency period to develop secondary malignancies as a result of RT exposure. The average age of patients in screening programs is So…. we are not talking about screening healthy children, teenagers, or even young adults. With a year latency period the risk is acceptable at these exposures, when weighed against the knowledge that one in one hundred of these patients has lung cancer.
year latency period to develop secondary malignancies from RT exposure
Average age of patients in screening trials is 62

45. Average age of patients in screening trials is 62
Radiation Exposure
LDCT
1 mSv
Years of annual lung screening
Mammogram
.7 mSv
Lumbar Spine Films
2 mSv 2
Diagnostic Chest CT
10 mSv 10
Triphasic CT AB/P
25 mSv 25
Background Exposure Colorado
3 mSv/year
11.8 mSv/year 3
11.8
Occupational Exposure
50 mSv/year 50
Transatlantic Flight
.1 mSv
10 flights = 1 LDCT
Here is a chart for comparison purposes. LDCT exposure is similar to a mammogram. A Lumbar spine film series is 2mSv or the equivalent of 2 years of annual LDCT scanning. Triphasic CT abd/pel is 25mSv. Background exposure is 3 mSv at sea level and 4.5mSv in Denver Colorado. Occupational exposure for a radiation worker such as myself is 50mSv, I am allowed each year to be exposed to the equivalent of 50 LDCT studies. A transatlantic flight is .1mSv such that 7 transatlantic flights equals 1 LDCT. Also an important consideration regarding radiation risk is the year latency period to develop secondary malignancies as a result of RT exposure. The average age of patients in screening programs is So…. we are not talking about screening healthy children, teenagers, or even young adults. With a year latency period the risk is acceptable at these exposures, when weighed against the knowledge that one in one hundred of these patients has lung cancer.
year latency period to develop secondary malignancies from RT exposure
Average age of patients in screening trials is 62

46. National Concerns/Criticisms
Increased radiation exposure
“False positives”
We are invasively treating indolent cancers
Cost to the system

47. ACR Adopted 6mm as minimum nodule size.
Ground glass opacity cutoff 2cm
Duration of nodule stability 3 months (decreased from 2 yrs)

48. National Concerns/Criticisms
Increased radiation exposure
“False positives”
We are invasively treating indolent cancers
Cost to the system

50. National Concerns/Criticisms
Increased radiation exposure
“False positives”
We are invasively treating indolent cancers
Cost to the system

53. Limitations of Analysis
1) Excluded 150 NLST participants from analysis (48 had lung cancer) due to not having adequate info to project survival
More in CT group (probably bias against CT)
2) Assumed CT screening program did not affect smoking status
3) This analysis performed with NSLT (not ACR)

54. Lung Cancer Updates
MANY advances in therapies with exciting things on horizon
Targeted therapy
Immunotherapy
Lung screening is one of the biggest advances (not yet happening)