WELCOME LUNG FORCE Expo San Diego, CA

Transcription

1 WELCOME 2016 LUNG FORCE Expo San Diego, CA 1

2 LUNG FORCE EXPO COMMITTEE CHAIR SANDIP PATEL, MD UC San Diego Health Moores Cancer Center 2

3 Fill every breath you take with hope - because every breath you take matters 3

4 AGENDA Lung Health and the Immune System E-Cigarettes: A Solution to Nicotine Addiction? Or Just Nicotine in Solution? Health Disparities in Asthma and COPD: Challenges to Non-Compliance 10:25 Break Exhibits Passport Activity Lung Cancer Screening: Maximizing Gain and Minimizing the Pandora s Box Effect CitiSense: Personal Mobile Air-quality Monitoring for Improving Personal Health and Informing Public Policy 12:00 LUNCH Exhibits Passport Activity 12:45 Breakout Sessions A -New Methods of Medication Delivery into the Lungs : Say Goodbye to the MDI B -Patient Empowerment Improving 3-day Readmission Outcomes 1:25 Break American Lung Association Programs and Resources Human Mircobiomes: How Gut Health Impacts Health* 4

5 COMMITTEE MEMBERS Sandip Patel, MD Committee Chair Theresa Cannizzaro, RRT Marc Fuster, MD Jodi McEdward, RRT, C-AE Luisa Monson, RN Philippe Montgrain, MD Tim Morris, MD Donna Murphy, RRT Valerie Naegele, RRT Nikki Reese, RRT Julie Ryu, MD Lucy von Buttlar Angela Wang, md Michael Welch, MD Peggy Wells, RRT SUPPORTERS Nellie Thatcher Perkins Foundation Apria Boston Scientific BBVA Compass Community Service Association (SDUSD) CSL Berhing CVS Health Pfizer RxPathways Kindred Hospital Medtronic Monaghan Medical Myriad My Plan UC San Diego Health 5

6 BE SOCIAL WITH US #lfexpo #lungforceexpo 6

7 LEARNING OBJECTIVES HEALTHCARE PROVIDER TRACK At the end of the LUNG FORCE Expo participants will be able to: 1.) Characterize the role the immune system plays in cancer, asthma, COPD, microbiome, and lung health. 2.) Identify the public health risks of e-cigarettes use. Describe the concerns of e-cigarette use in tobacco cessation. 3.) Recognize reasons for health disparities and barriers to non-compliance in their patients with asthma and COPD. 4.) Explain basic guidelines for lung cancer screening, including considerations and referral of patients in unique risk groups. 5.) Recognize the opportunity of personal air-quality monitoring for improving personal health and informing public policy. 6.) Define and demonstrate new types of inhaled delivery devices/ systems that have either arrived on the scene recently, or will likely appear soon in the future, that make delivering medication to the lungs for pulmonary diseases easier and/or better. 7.) Describe patient education and support programs and resources, lists benefits, and implement referral processes. 7

8 WELCOME TO LUNG FORCE EXPO 2016 Your Lungs, Your Immune System, And You Sandip Patel, MD Lung Expo 2016 Committee Chair Assistant Professor Medical Oncology, Hematology UCSD Moores Cancer Center 8

9 A COMMON THREAD, A COMMON PURPOSE THE IMMUNE SYSTEM IN LUNG HEALTH Whether talking about e-cigarettes and lung inflammation, asthma, lung cancer screening, air quality, or microbiomes The immune system plays a central role in preventing (and sometimes causing) lung disease Immunotherapy is the biggest breakthrough in cancer, and especially lung cancer 9

10 LUNG HEALTH IN THE US THE BURDEN OF THE IMMUNE SYSTEM ON LUNG HEALTH Cancer #2 cause of death Lung cancer kills 158,000 Americans a year COPD/Asthma #3 150,000 deaths a year Influenza and Pneumonia #8 57,000 deaths a year 365,000 deaths a year from lung related disease--- 1,000 deaths a day 10

11 Immunologic Synapses Within Tumor Microenvironment Tumor Cell IFN-γ mediated upregulation of tumor PD-L1 IFN-γ Tumor-associated fibroblast Stromal PD-L1 modulation of T cells IFN-γR Other NFκB P13K CD8+ cytoxic T lymphocyte M2 macrophage PD-L1/PD-1 mediated inhibition of tumor cell killing T reg cell IL-4/13 T h 2 T cell TGF-β Dendritic Cell T-cell polarization Priming and activation of T cells Immune cell modulation of T cells PD-L2 mediated inhibition of T H 2 T cells PD-1 PD-L1 PD-L2 T-cell receptor MHC-1 CD28 Shp-2 B7.1 Sznol M, et al. Clin Cancer Res. 2013;19:

12 APC or Tumor T Cell CD80/B7-1 CD86/B7-2 ICOSL/B7-H2 [CD275] CD70/TNFSF7 [CD27L] OX40L/TNFSF4 [CD252] 4-1BBL/TNFSF9 [CD137L] CD40/TNFRSF5 MHC CD80/B7-1 CD86/B7-2 PD-L1/B7-H1 [CD274] PD-L2/B7-DC [CD273] B7-H3 [CD276] B7-H4/VTCN1 HVEM/TNFRSF14 [CD270] GAL9 CD28 ICOS [CD278] CD27/TNFRSF7 OX40/TNFRSF4 [CD134] 4-1BB/TNFRSF9 [CD137] CD40L/TNFSF5 [CD154] TCR LAG3 [CD223] CTLA-4 [CD152] PD-1 [CD279]?? BTLA [CD272] CD160 TIM-3 2 nd Signal Activation 1 st Signal 2 nd Signal Inhibition 12

13 SP142 PD-L1 EXPRESSION LEVEL IN NSCLC TC3 and IC3 represent distinct populations with <1% overlap in NSCLC TC3 9% IC3 6% <1% PD-L1 TC3 PD-L1 IC3 TC2/3 18% 7% IC2/3 15% d TC1/2/3 9% 29% IC1/2/3 36% IC0 and TC0 26% IC=immune cells; TC=tumor cells Schmid P, et al. Poster. ESMO (abstr P269). 13

14 CHARACTERISTICS FOR TC3 AND IC3 NSCLC TUMORS Sclerotic Desmoplastic Associated with EMT Regulated by methylation Intrinsic PD-L1 regulation PD-L1 TC3 tumors exhibit a desmoplastic and sclerotic TME with low intra-epithelial and stromal IC TC3 PD-L1 TC3 vs IC3 NSCLC tumors have distinct tumor TME IC3 PD-L1 IC3 tumors represent immune-rich/cd8 high tumors Adaptive PD-L1 regulation Intra-epithelial/stromal IC Presence of T eff cells CD8 IHC Despite the differences in TME, both TC and IC predict for clinical benefit to atezolizumab IC=immune cells; TC=tumor cells; TME=tumor microenvironment Schmid P, et al. Poster. ESMO (abstr P269). 14

15 POPLAR: OVERALL RESPONSE AND DURATION OF RESPONSE 50 Atezolizumab (n = 144) Docetaxel (n = 143) ORR (confirmed; RECIST v1.1), % TC3 or IC3 TC2/3 or IC2/3 TC1/2/3 or IC1/2/3 TC0 and IC0 ITT ITT Atezolizumab (n = 21) Docetaxel (n = 21) Median duration of response, mo (95% CI) 14.3 (11.6, NE) 7.2 (5.6, 12.5) HR a (95% CI) 0.41 (0.18, 0.96) P value b Responders with ongoing response c, n (%) 12 (57%) 5 (24%) 15 15

16 RESPONSE RATE BY PD-L1 IHC EXPRESSION Therapy Histology PD-L1 IHC strata Nivolumab (anti-pd-1, BMS) Melanoma + - NSCLC + - Multiple (melanoma, RCC, NSCLC, CRC, mcrpc) + - ORR 44% 17% 67% 0% 36% 0% Pembrolizumab (anti-pd-1, Merck) Melanoma + - MPDL3280A (anti-pd-l1, Roche) NSCLC + - Multiple (melanoma, RCC, NSCLC, CRC, gastric) % 6% 67% 0% 39% 13% NSCLC + - Bladder % 15% 52% 11% Patel, Kurzrock Mol Canc Ther

17 WHY DO PD-L1 NEGATIVE PATIENTS RESPOND? Biopsy does not capture relevant tumor-immune infiltrate Biopsy too small Generally need core needle biopsy Akin to lymphoma Biopsy location Pleural/pericardial fluid cell blocks, bone lesions not helpful Biopsy timing relative to therapy PD-L1 immune expression? Alternative biomarkers needed Mutational burden and neoantigen diversity 17

18 NSCLC: A TALE OF TWO HISTOLOGIES Same drug: nivolumab Same disease: NSCLC Same setting: refractory, metastatic NSCLC Different histologies: squamous vs nonsquamous (mainly adenoca) 18

19 CHECKMATE 017: NIVOLUMAB VS DOCETAXEL IN PREVIOUSLY TREATED SQUAMOUS NSCLC Open-label, randomized phase III trial Stratified by previous paclitaxel therapy (yes vs no) and region Pts with stage IIIB/IV squamous NSCLC and ECOG PS 0-1 with failure of 1 previous platinum doublet chemotherapy (N = 272) Nivolumab 3 mg/kg IV q2w (n = 135) Docetaxel 75 mg/m 2 IV q3w (n = 137) Until disease progression or unacceptable toxicity Primary endpoint: OS Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression, safety, QoL Spigel DR, et al. ASCO Abstract Brahmer J, et al. N Engl J Med. 2015; [Epub ahead of print]. 19

20 Overall Survival (% of Patients) CHECKMATE 017: OS IN THE ITT POPULATION (SQUAMOUS) At Risk, n Nivolumab Docetaxel Mos Nivolumab (N = 135) Docetaxel (N = 137) Median OS mo (95% CI) 9.2 ( ) 6.0 ( ) Yr OS % of patients (95% CI) 42 (34-50) 24 (17-31) HR for death, 0.59 ( ) P < Nivolumab Docetaxel 0 0 No. of Deaths Spigel DR, et al. ASCO Abstract Brahmer J, et al. N Engl J Med. 2015;[Epub ahead of print]. 20

21 CHECKMATE 017: OS BY PD-L1 EXPRESSION (SQUAMOUS) OS BENEFIT SEEN WITH NIVOLUMAB VS DOCETAXEL INDEPENDENT OF PD-L1 EXPRESSION; SIMILAR TREND IN PFS, ORR Median OS by PD-L1 Expression Level,* Mos Nivolumab Docetaxel Unstratified HR (95% CI) Interaction P Value 1% < 1% ( ) 0.58 ( ).56 5% < 5% ( ) 0.70 ( ).47 10% < 10% ( ) 0.70 ( ).41 Not quantifiable 0.39 ( ) * PD-L1 expression measured in pre-treatment tumor biopsies with validated, automated immunohistochemical assay using PD-L1 antibody clone Spigel DR, et al. ASCO Abstract Brahmer J, et al. N Engl J Med. 2015; [Epub ahead of print]. 21

22 CHECKMATE 057: NIVOLUMAB VS DOCETAXEL IN PREVIOUSLY TREATED NONSQUAMOUS NSCLC Primary endpoint: OS Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression, safety, QoL Pts with stage IIIB/IV nonsquamous NSCLC and ECOG PS 0-1 who failed 1 prior platinum doublet chemotherapy ± TKI therapy (N = 582) Nivolumab 3 mg/kg IV q2w (n = 292) Docetaxel 75 mg/m 2 IV q3w (n = 290) Until disease progression or unacceptable toxicity Paz-Ares L, et al. ASCO Abstract LBA

23 Overall Survival (%) CHECKMATE 057: OS IN THE ITT POPULATION (NONSQUAMOUS) At Risk, n Nivolumab Docetaxel Time (Mos) yr OS rate = 39% mos, mo 1-yr OS rate = 51% Nivolumab (n = 292) 12.2 Nivolumab Docetaxel 9 5 Docetaxel (n = 290) HR = 0.73 (96% CI: 0.59, 0.89); P = Paz-Ares L, et al. ASCO Abstract LBA109. Reprinted with permission. 23

24 CHECKMATE 057: OS BY PD-L1 EXPRESSION (NONSQUAMOUS) SIMILAR INTERACTION RESULTS BASED ON BASELINE PD-L1 EXPRESSION OBSERVED FOR PFS AND ORR Median OS by PD-L1 Expression Level, mos Nivolumab Docetaxel Unstratified HR (95% CI) Interaction P Value 1% < 1% ( ) 0.90 ( ) % < 5% ( ) 1.01 ( ) % < 10% ( ) 1.00 ( ).0002 Paz-Ares L, et al. ASCO Abstract LBA109. Reprinted with permission. 24

25 THE PREVALENCE OF SOMATIC MUTATIONS ACROSS HUMAN CANCER TYPES LB Alexandrov et al. Nature 000, 1-7 (2013) doi: /nature

26 Mutational Landscape of Melanoma According to Clinical Benefit from Ipilimumab Treatment. Snyder A et al. N Engl J Med 2014;371:

27 Rizvi NA et al. Science 3/12/14 27

28 CAN APPLY SAME TECHNIQUES ACROSS TUMOR TYPES: NSCLC Rizvi NA et al. Science 3/12/14 28

29 Neoantigen clonal architecture and clinical benefit of immune checkpoint blockade Published by AAAS Nicholas McGranahan et al. Science 2016;science.aaf

30 NSCLC- Candidate neoantigens, neoantigen-specific T cell response, and response to pembrolizumab. Rizvi et al. Science

31 BIOMARKER ENRICHMENT- OS IN NSCLC WITH PEMBROLIZUMAB PD-L1 expression on tumor membrane 50% cutoff point Garon et al. NEJM

32 SUMMARY LUNG FORCE EXPO 2016 Cancer immunotherapy has revolutionized cancer treatment, with melanoma as the forerunner but NSCLC Anti-PD-1/PD-L1 therapies are revolutionizing oncology Durable responses in some patients Combination therapy likely needed PD-L1 IHC is an important part of the story Other biomarkers will be needed in conjunction with PD-L1 IHC The immune system is central to lung pathology- from cancer to asthma to COPD to pneumonia Lung Force Expo 2016: Your Lungs, Your Immune System, and You! 32

33 THANKS! Sandip Patel Lung Expo 2016 Committee Chair Assistant Professor Medical Oncology, Hematology UCSD Moores Cancer Center 33