Lung Cancer Stages, Treatments and Targeted Therapies
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Audio and slides for this presentation are available on YouTube: http://youtu.be/rt_O7m2eTYA David Barbie, MD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, discusses the stages of lung cancer, how the disease is treated, and new targeted therapies for patients. This presentation was originally given at Dana-Farber's "Living with Lung Cancer" forum on Nov. 2, 2013.
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Lung Cancer Stages, Treatments and Targeted Therapies
- 1. Lung Cancer: Stages, Treatments and Targeted Therapies David Barbie, M.D. Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute Assistant Professor of Medicine, Harvard Medical School November 2, 2013
- 2. Lung Cancer Incidence and Mortality in U.S. KRAS Mutation ~30% ~50% ~90%
- 3. Lung Cancer Stages and Treatments
- 4. Lung Cancer Stages and Treatments Stage 1: Localized
- 5. Lung Cancer Stages and Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Surgery, +/-chemotherapy
- 6. Lung Cancer Stages and Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Surgery, +/-chemotherapy Stage 3: Locally advanced Chemotherapy and radiation, +/- surgery
- 7. Lung Cancer Stages and Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Brain Surgery, +/-chemotherapy Stage 3: Locally advanced Chemotherapy and radiation, +/- surgery Bone Stage 4: Advanced/metastatic Chemotherapy +/- palliative radiation Liver Adrenals
- 8. Oncogenes are the Jammed Accelerators of Cancer Cells
- 11. BCR-ABL - BCR-ABL + Shtivelman et al. Nature 1985;315:550 Daley et al. Science 1990;247:824 Buchdunger et al. Cancer Res 1996;56:100 Deininger et al. Blood 1997;90:3691 Druker, BJ. Nat Med 2009;15:1149
- 12. Lynch et al. NEJM 2004;350:2129 Paez et al. Science 2004;304:1497
- 13. Mok et al. NEJM 2009;361:947
- 14. Better than chemotherapy, but tumors become resistant after 10-12 months Mok et al. NEJM 2009;361:947
- 15. Genomic complexity of lung cancer CML Lung Adenocarcinoma http://www.path.cam.ac.uk http://www.utoronto.ca/cancyto
- 16. Lung Cancer Then and Now Many different oncogenes can get jammed No known genotype 1984 - 2003 No known genotype 2004 Erlotinib X X 2009 Crizotinib 2012 Courtesy of Stephanie Cardarella, MD, DFCI Thoracic Oncology
- 17. Chemotherapy Targets the Engine, Targeted Therapy the Accelerator EGFR inhibitor ALK inhibitor BRAF inhibitor Carboplatin + Alimta or Taxol
- 18. DFCI Patient with NSCLC and BRAF mutation treated with Dabrafenib August 10, 2012 September 19, 2012 Courtesy of Stephanie Cardarella, MD, DFCI Thoracic Oncology
- 19. MSKCC Patient with NSCLC and BRAF mutation treated with Dabrafenib February 2012 June 2012 Courtesy of Gregory Riely, MD, Memorial Sloan-Kettering Cancer Center
- 20. KRAS is Difficult To Target Directly KRAS inhibitor – failed clinical trials
- 21. Alternatives to Targeting KRAS 1. Block known downstream pathways (between pedal and engine) Also failing in clinical trials
- 22. Alternatives to Targeting KRAS 1. Block known downstream pathways (between pedal and engine) XX Also failing in clinical trials X X
- 23. Alternatives to Targeting KRAS 2. Use genomics to identify currently unknown pathways needed for survival (that keep car from crashing) TBK1
- 24. CYT387 Impairs Viability of Lung cancer Cells A549 Lung Cancer Cells DMSO CYT387 (5mM)
- 25. Activity of CYT387 in Kras-driven Murine Lung Cancer Murine KRAS-Driven Lung Cancer CYT387 100mg/kg/d H Baseline H Week 16 Kwok Wong Travis Cohoon
- 26. Activity of CYT387 in Kras-driven Murine Lung Cancer H E pA ST T3 A B Uee n ad t t r 2m 5 µ C 2m 5 µ D Tor an a t el e xe o 2m 5 µ E 2m 5 µ F C an Yl e To 2m 5 µ 2m 5 µ
- 27. Alternatives to Targeting KRAS Blocking multiple unique pathways
- 28. Alternatives to Targeting KRAS Blocking multiple unique pathways X X X X
- 29. Activity of CYT387 in Kras-driven Murine Lung Cancer KrasLSL-G12D/WT;p53flox/flox model with established tumor burden *p<0.01 **p<0.0001 CYT387: 100 mg/kg/daily by oral gavage Selumetinib: 25 mg/kg/twice daily by oral gavage Kwok Wong Travis Cohoon
- 30. Activity of CYT387 in Kras-driven Murine Lung Cancer KrasLSL-G12D/WT;p53flox/flox model with established tumor burden *p<0.01 **p<0.0001 Treatment well tolerated other than initial gavage trauma CYT387: 100 mg/kg/daily by oral gavage Selumetinib: 25 mg/kg/twice daily by oral gavage Kwok Wong Travis Cohoon
- 31. Immunotherapy – “Immune Checkpoint Blockade”
- 32. Immunotherapy – “Immune Checkpoint Blockade”
- 33. Immunotherapy – “Immune Checkpoint Blockade” PD-L1 PD-L1 PD-L1
- 34. Immunotherapy – “Immune Checkpoint Blockade” T cell T cell PD1 PD1 PD-L1 PD-L1 PD-L1 PD1 T cell
- 35. Immunotherapy – “Immune Checkpoint Blockade” T cell X T cell PD1 X PD1 PD-L1 PD-L1 PD-L1 T cell X PD1
- 36. Immunotherapy – “Immune Checkpoint Blockade” T cell PD-L1 targeted drugs T cell X PD1 X PD1 PD-L1 PD-L1 PD-L1 T cell X PD1
- 37. Immunotherapy – “Immune Checkpoint Blockade” T cell T cell PD1 PD1 PD1 T cell
- 38. Immunotherapy – “Immune Checkpoint Blockade” T cell T cell PD1 PD1 PD1 T cell
- 39. Summary • Lung cancer can be treated with a combination of surgery, radiation, and chemotherapy depending on the stage
- 40. Summary • Lung cancer can be treated with a combination of surgery, radiation, and chemotherapy depending on the stage • We continue to develop new ways to target lung cancer more directly, with increasing success
- 41. Summary • Lung cancer can be treated with a combination of surgery, radiation, and chemotherapy depending on the stage • We continue to develop new ways to target lung cancer more directly, with increasing success • With combinations of these new targeted therapies the future is very bright