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The Latest in Targeted Therapy for Lung Cancer

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Geoffrey Oxnard, MD, discusses the latest research in targeted therapies and molecular testing to treat lung cancer.

This presentation was originally given as part of "Living with Lung Cancer: A Forum for Patients and Caregivers" on Nov. 14, 2015 at Dana-Farber Cancer Institute in Boston, Mass.

Published in: Health & Medicine
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The Latest in Targeted Therapy for Lung Cancer

  1. 1. Lung cancer targeted therapies and molecular testing Geoff Oxnard, MD Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute
  2. 2. Overview 1. What is a targeted therapy? 2. Picking a targeted therapy 3. Genotyping to find a target 4. Liquid biopsies instead of tumor biopsies
  3. 3. Cytotoxic chemotherapy • Aim is to induce unique toxicity against dividing cells • Inherently also toxic to healthy cells • Various categories we learn in pharmacology: – Anti-metabolites – Microtubule inhibitors – Alkylating agents – Topoisomerase inhibitors
  4. 4. Cytotoxic chemotherapy • More chemo is more toxic but not necessarily more effective • Chemotherapies are selected empirically • Prefer combinations of agents with non- overlapping toxicities: Drugs that impair bone marrow Drugs that cause neuropathy Carboplatin Docetaxel Gemcitabine Cisplatin Paclitaxel
  5. 5. Cytotoxic chemotherapy • Chemotherapy can be curative! – Chemosensitive cancers • Germ cell tumors • Lymphomas – Adjuvant therapy after surgery • NSCLC • Colorectal cancer • Breast cancer – Combined with radiation • Oropharyngeal cancers
  6. 6. What is “targeted therapy”? Empiric therapy: • Drugs you give to anyone who will tolerate and will gain some benefit Rationally-directed targeted therapy: • Drugs you give to patients who, in advance, you know will benefit
  7. 7. • Erlotinib is an oral EGFR tyrosine kinase inhibitor Hynes et al, Nature Reviews, 2005 EGFR EGFR What is “targeted therapy”?
  8. 8. Hynes et al, Nature Reviews, 2005 EGFR EGFR TKI • Erlotinib is an oral EGFR tyrosine kinase inhibitor What is “targeted therapy”?
  9. 9. Erlotinib for NSCLC • BR-21 study randomized patients with previously treated metastatic lung cancer to either erlotinib (EGFR TKI) or placebo Shepherd et al, NEJM, 2005
  10. 10. Baseline Day 6 Vince Miller, Memorial Sloan-Kettering Cancer Center Erlotinib for NSCLC
  11. 11. Erlotinib for NSCLC Erlotinib is either: 1. A drug that helps all lung cancer patients, but just a little bit 2. A drug that helps few lung cancer patients, but with a major effect
  12. 12. Erlotinib for NSCLC Erlotinib is either: 1. A drug that helps all lung cancer patients, but just a little bit 2. A drug that helps few lung cancer patients, but with a major effect Which would you prefer?
  13. 13. 2009 2012 2004 No known genotype 1984 - 2003 No known genotype Stephanie Cardarella, Dana-Farber Cancer Institute Cancer genetics
  14. 14. We use cancer genetics to pick a targeted therapy: Erlotinib Afatinib Sunitinib Crizotinib Alectinib Dabrafenib Osimertinib CLINICAL TRIALS Cancer genetics
  15. 15. We use cancer genetics to pick a targeted therapy: Cancer genetics
  16. 16. • What characteristics are we looking for in a great targeted therapy? Picking a targeted therapy
  17. 17. • What characteristics are we looking for in a great targeted therapy? Picking a targeted therapy Pretreatment After 6 months
  18. 18. • What characteristics are we looking for in a great targeted therapy? Picking a targeted therapy
  19. 19. • Molecular analysis of tumor DNA allows identification of therapeutic targets Tumor genotyping
  20. 20. • Molecular analysis of tumor DNA allows identification of therapeutic targets • Next-generation sequencing is a single assay covering >300 genes which can comprehensively characterize a cancer Tumor genotyping
  21. 21. • New approaches can at times allow noninvasive analysis of a blood specimen • We are studying the free floating tumor DNA circulating in plasma Liquid biopsy
  22. 22. • In patients with EGFR-mutant lung cancer, we can detect response and resistance EGFR exon 19 del EGFR T790M Patient 1 Patient 2 Progression on CT Progression on CT Liquid biopsy
  23. 23. • In patients with EGFR-mutant lung cancer, we can detect response and resistance EGFR exon 19 del EGFR T790M Patient 1 Patient 2 Progression on CT Progression on CT Liquid biopsy
  24. 24. • In patients with EGFR-mutant lung cancer, we can detect response and resistance EGFR exon 19 del EGFR T790M Patient 1 Patient 2 Progression on CT Progression on CT Liquid biopsy
  25. 25. DAY 0: CT shows marked progression on erlotinib, plasma drawn DAY 25: Report from rebiopsy genotyping shows EGFR T790M DAY 73: CT demonstrates a radiographic response DAY 1: cfDNA genotyping detects 806 copies/ml of EGFR T790M DAY 31: Patient starts treatment with an investigational EGFR inhibitor Sacher et al, ASCO, 2014
  26. 26. • We are working to improve our liquid biopsy technologies in hopes of facilitating rapid delivery of targeted therapies to as many patients as possible Liquid biopsy
  27. 27. Living with lung cancer • 3 rules to living with lung cancer 1. Don’t lose weight • Maximize calorie intake, even junk food 2. Don’t act sick • Even when you feel sick, go do something (and then go take a nap) 3. Don’t be a tough guy • If your symptoms aren’t well controlled, call us and we’ll adjust your medications
  28. 28. Living with lung cancer • Lung cancer changes your life • This is a serious disease, but we can’t know an individual patient’s prognosis until treatment starts • Try to accept the uncertainty: – Make priorities for yourself – Make the most of good days – Try to turn bad days into good days

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