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Goals of Care: Changing the Game for Lung Cancer Patients

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In this webinar:

Dr. Krista Noonan is a medical oncologist specializing in thoracic and genitourinary malignancies at BC Cancer, Surrey Centre. Her research interests focus on thoracic and genitourinary malignancies and health services research. On Thursday, February 27, join Dr. Noonan as she: - Reviews the advancements in systemic therapy in lung cancer over the past decade - Highlights how the advancements in systemic therapy have dramatically improved quality of life and length of life.

View the video: https://youtu.be/3DaUwQ8ab44

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Goals of Care: Changing the Game for Lung Cancer Patients

  1. 1. Goals of Care: Changing the Game for Lung Cancer Patients Krista Noonan, MD FRCPC Medical Oncologist, BC Cancer Surrey Clinical Assistant Professor, UBC February 29, 2020
  2. 2. Disclosures • Advisory Boards: Astra Zeneca, BMS, Merck, Novartis, Pfizer • Speakers Bureau: Merck
  3. 3. Objectives • Outline the incidence and survival of lung cancer Nationally • Discuss Goals of Care for Lung Cancer Patients • Review the critical studies showing how we have improved the lives of patients with lung cancer
  4. 4. Cancer is the leading cause of death in Canada Canadian Cancer Society Statistics 2017
  5. 5. Lung Cancer is the leading cause of cancer death in Canada 1 in 11 men will develop lung cancer during his lifetime and 1 in 14 will die from it 1 in 14 women will develop lung cancer during her lifetime and 1 in 17 will die from it Canadian Cancer Society Statistics 2017
  6. 6. Most patients are diagnosed with Stage 4 Disease Canadian Cancer Statistics 2018 *excludes Quebac
  7. 7. There is reason for optimism! Canadian Cancer Statistics 2017
  8. 8. Goals of Care
  9. 9. Lung Cancer Prevention • Smoking cessation – 85% of lung cancers are associated with smoking tobacco • Reduce exposure to second-hand smoke • Get your home checked for radon • Avoid asbestos exposure
  10. 10. Smoking Cessation Saves Lives Canadian Cancer Society 2017
  11. 11. Lung Cancer screening with low dose CT reduced deaths from lung cancer 1 Aberle DR, N Engl J Med. 2011; 365:395; 2 deKoning H, N Engl J Med. 2020; NLST1 NELSON2 We eagerly await implementation of population-based screening programs
  12. 12. Staging/Extent of Spread of Cancer Lung Cancer Canada Potentially Curable IncurableCurable
  13. 13. Stage Shift with Lung Cancer Screening NELSON study- De Koning et al. NEJM 2020 Low dose CT screening: 60% diagnosed with Stage 1 disease 10% diagnosed with Stage 4 disease No CT screening: 13% diagnosed with Stage 1 disease 46% diagnosed with Stage 4 disease
  14. 14. Goals of Care Influenced by several factors • Patient values and preferences* • Stage of disease • Functional Status • Comorbities
  15. 15. Goals of Care Discussions They should Not: • Code status discussion • Focus on death and dying • Delayed until crisis • Pressured • Uninformed • Transactional • Adversarial They should: • Patient-centric, value-driven • Begin early in the diagnosis • Focus on the entire trajectory of the illness (treatments, intensity of care, and advanced care planning) • Exploratory/conversational • Longitudinal
  16. 16. Foundational Principles of Effective Communication • Explore the patient’s understanding of their disease • Ask patients how much information they wish to hear eg. Diagnosis, prognosis, treatments • Cure versus quality of life versus length of life • Risks and benefits of each treatment, clinical trials • Timely, honest and empathic responses foster trust
  17. 17. Stage 1-3 Disease Goals of Care: Potential Cure
  18. 18. Treatment of Early Stage Disease • Resection followed by adjuvant chemotherapy • Sadly, chemotherapy only provides ~5% reduction in risk of death • Focus of current research – Using immunotherapy adjuvantly (after surgery to try to eradicate any microscopic cancer cells left behind) – Using immunotherapy neoadjuvantly (before surgery to shrink the cancer; decrease microscopic cells)
  19. 19. Phase 3 Adjuvant Studies • ANVIL- Nivolumab • BR31- Durvalumab • PEARLS- Pembrolizumab NB- select studies; www.clinicaltrials.gov.ca for complete list
  20. 20. Neoadjuvant Studies • AEGEAN- Durvalumab-Chemo • Checkmate 816- Nivolumab-chemo/nivolumab- ipilimumab • ImPower030- Atezolizumab-chemo • KEYNOTE 671- Pembrolizumab-chemo • NCT04025879- Nivolumab-chemo NB- select studies; www.clinicaltrials.gov.ca for complete list
  21. 21. Stage 3 unresectable • This was a large area of need • Concurrent chemoradiotherapy • Historically only 30-40% of patients received curative intent chemoRT – This may change in screen detected stage 3 lung cancers • 5-year OS rate ~20%
  22. 22. How does Immunotherapy work?
  23. 23. PACIFIC: Durvalumab Improves Survival
  24. 24. Stage 4 Disease Goals of Care: Quality of Life and Length of Life
  25. 25. Bow Tie model of Palliative Care Pippa Hawley Canadian Virtual Hospice 2015 www.virtualhospice.ca
  26. 26. Palliative Care Improves Survival and decreases symptom burden Temel et al. NEJM 2010
  27. 27. Huge Paradigm Shifts resulting in dramatic treatment improvements over the past decade
  28. 28. Advanced NSCLC: Before 2010 NSCLC Chemotherapy
  29. 29. 2002- Overall Survival was only 8 months Schiller, NEJM 2002
  30. 30. Stage 4 Disease • Previously, only 30% of patients received treatment • Only option was chemotherapy • Reasons: Poor performance status, patient choice, Therapeutic Nihilism, Co-morbidities, toxicity of treatments
  31. 31. Noonan K, Tong KM, Laskin J, et al. Referral patterns in advanced NSCLC: impact on delivery of treatment and survival in a contemporary population based cohort. Lung Cancer. 2014;86:344‐349. • Only 54% of patients were referred to Medical oncology • Only 30% of patients received chemotherapy
  32. 32. Cancer, Volume: 121, Issue: 15, Pages: 2562-2569, First published: 17 April 2015, DOI: (10.1002/cncr.29386)
  33. 33. 2009- EGFR-TKI Improved Response rates in EGFR mutated NSCLC
  34. 34. 2009- EGFR-TKI Improved Progression Free Survival in NSCLC
  35. 35. Lung Driver Mutations Adapted from Chan BA, Hughes BGM. Transl Lung Cancer Res 2015.
  36. 36. Advanced NSCLC: 2020 NSCLC Driver mutation EGFR+: Osimertinib ALK+: Alectinib BRAF+: Dabrafenib and Trametinib? ROS1+: Crizotinib PDL1 TPS ≥ 50% Pembrolizumab PDL1 TPS <50% Chemotherapy + Pembro 1st Line Stage 3 NSCLC (Durvalumab) SCLC (Atezolizumab)
  37. 37. Molecular subtypes in NSCLC 1. Adapted from Bubendorf L, Lantuejoul S. Eur Respir Rev. 2017 Jun 28;26(144). 2. Chan BA, Hughes BGM. Transl Lung Cancer Res 2015;4(1):36- 54. Alteration Occurrence (%) KRAS mutation 25 EGFR mutation 10 ALK fusion 4 ROS1 fusion 1.9 RET fusion 0.9 NTRK1 fusion 1 HER2 mutation 3 BRAF mutation 3 PI3KCA mutation 2 HRAS mutation 1 NRAS mutation 1 AKT mutation 1.1 MET exon 14 mutation 3 MAP3K1 mutation 1 Unknown 42 Adenocarcinoma1 Alteration Occurrence (%) FGFR1 amplification 22 DDR2 mutation 4 PI3KCA 33 MET amplification 5 MET mutation 1 BRAF mutation 2 Other or unknown 33 Squamous cell carcinoma1 Up to 30% of lung adenocarcinoma have a known oncogenic driver mutation2
  38. 38. Targeted therapies have improved clinical outcomes in lung cancer patients Kris MG, Johnson BE, Berry LD, et al. JAMA 2014; 311:1998–2006. • Lung Cancer Mutation Consortium Survival by Group. • Patients with an oncogenic driver mutation who did and did not receive targeted therapy, and patients without an oncogenic driver. 0.8 0.6 0.4 0.2 0 1.0 10 2 3 4 5 No. at risk Patients with oncogenic driver No targeted therapy Target therapy Patients with no driver 318 260 360 205 225 250 64 72 59 110 143 122 43 36 36 20 23 23 Log-rank P<.001 Years SurvivalProbability Target therapy No driver No targeted therapy
  39. 39. Recommended Testing Salgia, Future Oncol 2015 PDL1 +
  40. 40. Why does identifying a driver mutation matter?
  41. 41. 37 yo M Asian Never-smoker • Presented with SOB x 1/12 and hip pain 10/10 • Pain was so bad he was wheelchair bound • ECOG performance status 3, bx lung adenocarcinoma • I only had the ALK, ROS1, and PDL1 back when I saw him in consult. All were negative • He was too unwell for chemo, but I discussed that if he has an EGFR mutation then he could receive a pill form of therapy
  42. 42. Imaging
  43. 43. FLAURA Osimertinib (3rd gen TKI) > 1st gen TKI Improves PFS and OS Better QOL Brain penetration BC Cancer Funded as of Jan 2020 Planchard et al, ELCC 2018
  44. 44. 3 months after Osimertinib
  45. 45. 3 months after Osimertinib
  46. 46. Advanced NSCLC: 2020 NSCLC Driver mutation EGFR+: Osimertinib ALK+: Alectinib BRAF+: Dabrafenib and Trametinib? ROS1+: Crizotinib PDL1 TPS ≥ 50% Pembrolizumab PDL1 TPS <50% Chemotherapy + Pembro 1st Line Stage 3 NSCLC (Durvalumab) SCLC (Atezolizumab)
  47. 47. Advanced NSCLC PDL1>=50%: 3-yr OS rate 44% Reck et al. WCLC 2019
  48. 48. QOL data for KEYNOTE-024
  49. 49. 2002- Overall Survival was only 8 months Schiller, NEJM 2002
  50. 50. Advanced NSCLC: 2020 NSCLC Driver mutation EGFR+: Osimertinib ALK+: Alectinib BRAF+: Dabrafenib and Trametinib? ROS1+: Crizotinib PDL1 TPS ≥ 50% Pembrolizumab PDL1 TPS <50% Chemotherapy + Pembro 1st Line Stage 3 NSCLC (Durvalumab) SCLC (Atezolizumab)
  51. 51. Why is the use of IO so meaningful? 1. Quality of life/safety 2. Durability of response 3. Length of life 4. ? Cure for stage 4 disease
  52. 52. Summary • Lung cancer remains the cancer with the highest incidence and mortality in Canada • Goals of Care discussions that patient-centered, empathetic, honest yet instills hope are foundational • Assessment of driver mutations, PDL1 allows us to more precise with our treatments • Dramatic advancements in treatments improve cure, quality of life and length of life of our lung cancer patients
  53. 53. Questions?
  54. 54. Canadian Cancer Survivor Network Contact Info 1750 Courtwood Crescent, Suite 210 Ottawa, ON K2C 2B5 Telephone / Téléphone : 613-898-1871 E-mail: jmanthorne@survivornet.ca or info@survivornet.ca Website: www.survivornet.ca Twitter: @survivornetca Facebook: www.facebook.com/CanadianSurvivorNet Instagram: @survivornet_ca Pinterest: http://pinterest.com/survivornetwork/

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