LVRS and Endobronchial Therapy for Emphysema: Is it Still Viable? Malcolm M. DeCamp, MD Fowler McCormick Professor of Surgery Feinberg School of Medicine Chief, Division of Thoracic Surgery
Disclosures Consultant Covidien Mansfield, MA Consultant Portaero Cupertino, CA Advisory Bd PneumRx Mountain View, CA
Food for Thought CMS payment for LVRS: 2009 < 200 cases Barriers BLVR JCAHO Educational Void Apathy
100 NOTT Study Patient Surviving 80 24-hour oxygen % 60 40 20 Nocturnal oxygen 0 0 6 12 18 24 30 36 42 Duration of Treatment (months) Ann Intern Med 1980;93:391-98
NETT History Randomized 1218 patients; identified subgroups Survival Exercise capacity Quality of life Median follow-up of 29 mos (2.4 yrs) as of Dec 02 Only 60% of patients reached 2 yr testing mark
Outcomes Survival Exercise Quality of Life Cost Effectiveness
Probability of death 1.0 0.8 0.6 Overall P=0.02 RR = 0.85 Mortality All Patients Medical P 0.4 2 yr =0.48 LVRS 0.2 P 5 yr =0.02 0.0 0 1 2 3 4 5 6 7 8 Years after randomization 608 526 496 454 352 227 122 29 LVRS 610 564 507 441 335 210 99 29 Medical
WHO?
Independent Predictors (1) Distribution of emphysema Upper-lobe vs non upper-lobe predominance P for interaction = 0.02 (2) Post rehab exercise capacity Gender corrected low versus high capacity P for interaction = 0.01 Four subgroups based on combination P for interaction = 0.004
NETT Subgroups All Patients N = 1218 Non High Risk Patients N = 1078 High Risk Patients LVRS N = 140 Upper Lobe Low Exercise N = 290 Upper Lobe High Exercise N = 419 Non Upper Lobe Low Exercise N = 149 Non Upper Lobe LVRS High Exercise N = 220
Mortality Upper Lobe / Low Exercise RR = 0.57
Exercise Formal cycle ergometry Threshold > 10 watts (2 x MCID) 0.5, 1, 2 and 3 yrs
Exercise Improvement Upper Lobe / Low Exercise LVRS Medical % with > 10 watt gain 50 40 30 20 10 0 42% 6% 30% 21% 2% 0% Year 1 2 3 No. pts. 118 126 118 126 86 92 P <0.001 <0.001 <0.001
Quality of Life St George s Respiratory Questionnaire Threshold > 8 units (2 x MCID) 0.5, 1, 2, 3, 4 and 5 yrs
SGRQ Improvement Upper Lobe / Low Exercise LVRS Medical unit decline % with > 8 60 50 40 30 20 10 0 52% 44% 29% 7% 10% 9% 15% 6% 19% 0% Year 1 2 3 4 5 No. pts. 139 151 129 138 103 114 71 77 26 33 P <0.001 <0.001 <0.001 0.11 0.01
HOW?
Mortality by Surgical Approach All Patients
LVRS: MS vs. VATS Maximal Work (Watts) Pulmonary Function (%FEV1) 6 Minute walk (% Baseline)
LVRS: MS versus VATS MS VATS P Hospitalization $38,577 $30,350 P<0.01 6 months care $60,199 $49,638 P<0.01
MS vs VATS VATS provides. (1) earlier recovery (2) at a lower cost than MS
Years from RZ Cost-Effectiveness of LVRS: Subgroups Upper lobe/ Low exercise Projected Cost per QALY Gained Upper lobe/ High exercise Non upper lobe/ Low exercise 5 years* $77,000 $170,000 $225,000 10 years # $48,000 $40,000 $87,000 Future costs and QALYs discounted at 3% per year after year 1 * Observed Costs # Projected costs based on 5 yr F/U
Cost-Effectiveness Ratios: Selected Thoracic Surgical Procedures Intervention $ per QALY CABG $8,300 to $64,000 Heart Transplantation $65,000 Implantable Defibrillator $47,000 Lung Transplantation LVRS (Non Hi Risk, UL) $133,000 to $216,000 (5 yr) $124,000 (within trial) (10 yr) $44,000 (projected)
Conclusions In pts with upper lobe emphysema LVRS improves Survival Exercise capacity QOL Functional improvements decline over 3-5 years Despite this decline, the LVRS patients maintain clinical advantage over the medical cohort throughout 5 years of follow-up
Clinical Inference Based on NETT: LVRS should be strongly considered for all advanced emphysema patients with upper lobe predominant disease. Grade of Evidence = A
LVRS : What is the Denominator? ~ 15 % Akuhotra et al Ann Thorac Surg 2012 in press
Post-NETT LVRS Columbia Adopted NETT inclusion/exclusion criteria UL predominant emphysema Pre-selection pulmonary rehab Bilateral VATS Multi-disciplinary team Outcomes Changes in BODE
Columbia Post-NETT LVRS N = 49 2004-2009 Mean age 62.5 yrs 65 % female Mean FEV1 25% pred Mean DLCO 27% pred No operative mortality Survival 1 year 98 % 3 year 95 % Function 2.3 point improvement in BODE @ 1 year Supplemental O2 use preop 62% - postop 41% Ginsberg et al, Ann Thorac Surg 2011
Bronchoscopic Treatments Options Emphasys Zephyr Endobronchial Valve (EBV ) Spiration Intra-bronchial Valve (IBV ) Airway bypass, Broncus Technologies (Exhale DES) Aeris AeriSeal Endoscopic LVR (ELVR) Uptake Medical Thermal Vapor Ablation (BTVA ) PneumRx Lung Volume Reduction Coil (LVRC)
EBV TM IBV
Airway Bypass: Overview Broncus Technologies, Inc. Bronchoscopic intervention for homogeneous emphysema Extra-anatomic transbronchial pathways for trapped gas to escape Reduce hyperinflation Decrease in volume of trapped gas Increase in inspiratory muscle strength Reduced dyspnea and improved QOL
Established Airway Bypass
EASE Trial Exhale Airway Stents for Emphysema Controlled, double-blind, randomized, multi-center pivotal study Sham control arm 2:1 randomization (treatment:sham) 225-315 patients (Bayesian/adaptive statistics) No consistent, sustained benefit Shah et al Lancet September, 2011
AeriSeal - Device Description Sealant flows into the alveolar compartment as a liquid foam, polymerizes and seals the target area Small airways and collateral channels are obstructed Gas in the sealed area is absorbed leading to volume reduction Slide Courtesy of: Ed Ingenito, MD PhD Aeris Therapeutics Woburn, MA
Response Pattern HI at -910 = 2.03 BASELINE WEEK 12 WEEK 48 FEV1=0.78L FVC = 2.55L FEV1 = 1.31L FVC = 3.15 FEV1 = 1.29L FVC = 3.79L NEUMOMADRID Slide Courtesy of: Ed Ingenito, MD PhD Aeris Therapeutics Woburn, MA
6 Month Efficacy vs LVRS All patients AeriSeal System Therapy n=18 LVRS NETT All patients** n=454 Control NETT All patients** n=540 FEV 1 +31.2 ± 36.6%* +28.5 ± 33.6%* -1.8 ± 15.7% FVC +15.6 ± 20.3%* +16.8 ± 27.8%* -2.1 ± 15.4% RV/TLC -8.5 ± 12.3%* -13.2 ± 13.1%* 1.8 ± 9.1% 6MWT 11.8 ± 57.5 m 14.4 ± 70.9 m* -27.2 ± 57.3 m* MRCD -0.33 ± 0.77 U ND ND DLco 12.7 ±16.4%* - - SGRQ -8.0 ± 17.2 U* -11.2 ± 15.1 U* 2.0 ± 10.4 U ND: not done as part of study *p < 0.05 **Excludes High Risk NETT patients Slide Courtesy of: Ed Ingenito, MD PhD Aeris Therapeutics Woburn, MA
RePneu Lung Volume Reduction Coil (LVRC) Self-actuating Nitinol implant
RePneu LVRC Summary of Efficacy Results for Pilot Phase II FEV1 RV 6MWT SGRQ Change from Baseline +17.5% -11% +28% (71m) -16 points MCID: 12% MCID: 10% MCID: 48m MCID: -4 pnts. Responder Rate 73% 73% 1 82% 2 Results from Pilot Phase II OUS Study data on file at PneumRx 1 73% of patients showed significant improvement in exercise capacity as defined by an increase of greater than 25 meters in 6MWT at 6 months post treatment of the second side 2 82% of patients showed significant improvement in quality of life as defined by a decrease of greater than 4 points in SGRQ at 6 months post treatment of the second side
Bronchoscopic Treatment Options Emphasys Zephyr Endobronchial Valve (EBV ) Denied approval by FDA, sold to PulmonX Spiration Intra-bronchial Valve (IBV ) Pivotal trial results pending Airway Bypass EASE TM pivotal study showed no sustainable benefit Aeris AeriSeal (ELVR) Pivotal trial approved by FDA PneumRx Lung Volume Reduction Coil (LVRC) Pivotal trial imminent Uptake Medical Thermal Vapor Ablation (BTVA ) Pilot studies ongoing
LVRS/BLVR are viable therapies LVRS is safe and effective Upper lobe disease LVRS appropriate for subset (~15%) GOLD III-IV emphysema LVRS is under-utilized BLVR alternatives remain investigational Less morbid, may apply to other phenotypes Improved collaboration with pulmonology Direct patient advocacy