OA 17.06 Updated Analysis of KEYNOTE-024: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC With PD-L1 TPS ≥50%

November 2017 were observed in patients receiving nivolumab maintenance compared with the September 2014 database lock. ORR was 46%. Median duration of response was 10.4 mo (95% CI: 5.1, 26.3). Median PFS was 6.0 mo (95% CI: 4.8, 8.3). Median OS was 19.2 mo (95% CI: 14.1, 23.8), and the 3-year OS rate was 25%. ORR and OS were similar in patients with tumor PD-L1 expression <1% (n¼23) vs 1% (n¼23): ORR 48% vs 52%; median OS 19.2 mo (95% CI: 12.2, 23.8) vs 20.2 mo (95% CI: 10.9, 27.2). The 3-year OS rate was 22% in both PD-L1 expression subgroups. Conclusion: Nivolumab plus chemotherapy resulted in prolonged survival in a subset of patients, with a 3-year OS rate of 25%. In all patients, ORR and OS were similar irrespective of tumor PD-L1 expression. These results support further evaluation of nivolumabchemotherapy combinations as first-line treatment for advanced NSCLC, which are being explored in CheckMate 227 (NCT02477826). Keywords: Long-term, NSCLC, PD-L1

OA 17.05 IFCT-1502 CLINIVO: Real-Life Experience with Nivolumab in 600 Patients (Pts) with Advanced NonSmall Cell Lung Cancer (NSCLC) O. Molinier,1 C. Audigier-Valette,2 J. Cadranel,3 I. Monnet,4 J. Hureaux,5 W. Hilgers,6 E. Fauchon,7 E. Fabre,8 B. Besse,9 P. Brun,10 D. Coëtmeur,11 E. Quoix,12 P. Mourlanette,13 F. Barlesi,14 S. Bordenave-Caffre,15 T. Egenod,16 P. Missy,17 F. Morin,18 D. Moro-Sibilot,19 N. Girard20 1Pneumology, Centre Hospitalier Du Mans, Le Mans/FR, 2Pneumology, Centre Hospitalier Toulon SainteMusse, Toulon/FR, 3Service de Pneumologie, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris/FR, 4Pneumologie, Chi Créteil, Créteil/FR, 5Pôle Hippocrate, CHU Angers, Angers/FR, 6Oncologie Médicale, Institut Sainte Catherine, Avignon/FR, 7Cabinet Médical de Pneumologie, Saint Julien En Genevois/FR, 8Medical Oncology, Hôpital Européen Georges Pompidou (Hegp), Assistance Publique Hôpitaux de Paris (Ap-Hp), Paris, France, Paris/FR, 9Department of Cancer Medicine, Gustave Roussy, Villejuif/FR, 10Pneumologie, Ch Valence, Valence/FR, 11 Service de Pneumologie Et Oncologie Thoracique, Ch de Saint Brieuc, Saint Brieuc/FR, 12Service de Pneumologie - Pôle de Pathologie Thoracique, Nhc, CHU Strasbourg, Strasbourg/FR, 13Pneumologie, Clinique Des Cèdres, Cornebarrieu/FR, 14Multidisciplinary Oncology & Therapeutic Innovations, Aix Marseille University, Marseille/FR, 15 Pneumologie, Hôpital Laennec, CHU de Nantes, Nantes/FR, 16Unité D’Oncologie Thoracique Et Cutanée, CHU Limoges, Hopital Dupuytren, Limoges/FR, 17French Cooperative Thoracic Intergroup (Ifct), Paris/FR, 18 Clinical Research Unit, French Cooperative Thoracic Intergroup (Ifct), Paris/FR, 19Clinique de Pneumologie Et Oncologie Thoracique, CHU Grenoble-Alpes, La Tronche/FR, 20Institut Du Thorax Curie-Montsouris, Institut Curie, Paris/FR Background: Nivolumab is a standard option for second-line treatment in pts with advanced NSCLC. Real-life data are lacking regarding the efficacy of nivolumab and post-nivolumab treatment. Method: This analysis included the first 600 consecutive pts with stage IIIB/IV NSCLC who received 1 dose of nivolumab 3mg/kg q2w through the French EAP from 01/2015 for Squamous (Sq) and 06/2015 for Non-Sq NSCLC, until 08/2015. Result: Median age was 64 yo, there were 409 (68%) men, 521 (87%) smokers, 478 (80%) PS0/1 pts, 230 (38%) Sq and 370 (62%) Non-Sq NSCLC, 130 (22%) pts with brain metastases. Nivolumab was administered as 2nd/3rd/4th-line for 26%/33%/ 41% pts, respectively. Best response was PR/SD/PD for 17%/30%/ 37% of patients, respectively, with 16% not assessable. Toxicities occurred in 187 (31%) pts, including 10% grade 3 events. After a median follow-up of 22.1 (95% CI 21.6-22.6) months, median PFS and OS from the initiation of nivolumab were 2.1 (95%CI 1.9-2.3) and 9.5 (95%CI 8.4-10.8) months, respectively. In the 92 pts with PS2 at

Abstracts

S1793

initiation of nivolumab, PR/SD rates were 7%/28%; median OS was 3.6 (95%CI 2.7-5.2) months. A total of 130 pts had brain metastases at initiation of nivolumab: PR/SD rates were 12%/25%; median OS was 6.6 (95%CI 3.8-8.3) months. Post-nivolumab treatment was administered to 262 (44%) pts, and mostly consisted of gemcitabine (19%), docetaxel (18%), paclitaxel (14%), erlotinib (12%), vinorelbine (9%), platin-based doublet (8%), or pemetrexed (8%). Access to post-nivolumab treatment was higher in PS0/1 vs. PS2 pts (48% vs. 23%, p<0.001), but was not different according to histology or treatment line or disease control with nivolumab. Best response to post-nivolumab treatment was PR/SD/PD for 15%/42%/42% of pts, respectively. In the whole cohort, median post-nivolumab OS was 4.0 (95%CI 2.84.6) months, and was significantly higher in case of PR to nivolumab (HR¼0.38; 95%CI 0.23-0.64; p<0.001), and if subsequent treatment was delivered (HR¼0.30; 95%CI 0.24-0.38; p<0.001); median postnivolumab OS in pts receiving post-nivolumab treatment was 7.5 (95% CI 6.8-8.7) months, and did not differ based on histology or treatment line. Conclusion: Efficacy and safety of nivolumab was in line with available data. Post-nivolumab treatment may be delivered in many pts, including pts with PS2 and brain metastases, with favorable impact on response and OS. Data on the whole cohort of 900 pts enrolled in the EAP will be presented. Keywords: chemotherapy, non-small cell lung cancer, Nivolumab

OA 17.06 Updated Analysis of KEYNOTE-024: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC With PD-L1 TPS 50% J. Brahmer,1 D. Rodríguez-Abreu,2 A. Robinson,3 R. Hui,4 T. Cs} oszi,5 A. Fülöp,6 M. Gottfried,7 N. Peled,8 A. Tafreshi,9 S. Cuffe,10 M. O’Brien,11 S. Rao,12 K. Hotta,13 A. Riccio,14 J. Yang,14 M.C. Pietanza,14 M. Reck15 1Medical Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/MD/US, 2 Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas/ES, 3Cancer Centre of Southeastern Ontario, Kingston, ON/CA, 4 Department of Medical Oncology, Westmead Hospital and the University of Sydney, Sydney/AU, 5Jász-Nagykun-Szolnok County Hospital, Szolnok/ HU, 6Országos Korányi Pulmonológiai Intézet, Budapest/HU, 7Oncology Department, Lung Cancer Unit & Lung Cancer Research Lab, Meir Medical Center, Kfar-Saba/IL, 8Davidoff Cancer Center, Tel Aviv University, Petah Tikva/IL, 9Oncology, Southern Medical Day Care Centre, Wollongong/NSW/AU, 10Thoracic Oncology Research Group, St. James’s Hospital & Trinity College Dublin, Dublin/IE, 11Medical Oncology, Royal Marsden Hospital, Sutton/GB, 12Medstar Franklin Square Medical Center, Baltimore, MD/US, 13Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama/JP, 14Clinical Sciences and Study Management, Merck & Co., Inc., Kenilworth, NJ/US, 15Lung Clinic Grosshansdorf, Airway Research Center North (ACRN), Member of the German Center for Lung Research (DZL), Grosshansdorf/DE Background: KEYNOTE-024 (ClinicalTrials.gov, NCT02142738) is a multicenter, international, phase 3, randomized, open-label, controlled trial of treatment with the anti‒PD-1 antibody pembrolizumab vs platinum-based chemotherapy as first-line therapy for patients with advanced NSCLC of any histology with PD-L1 tumor proportion score (TPS) 50% and without EGFR mutations or ALK translocations. Results from the primary analysis of KEYNOTE-024 demonstrated that after a median follow-up of 11.2 months, pembrolizumab significantly improved PFS (HR¼0.50; P<0.001) and OS (HR¼0.60; P¼0.005) and was associated with a lower rate of treatment-related AEs compared with chemotherapy. Method: Patients were randomly assigned to receive either 35 cycles of pembrolizumab 200 mg every 3 weeks or 4e6 cycles of investigator’s choice of carboplatin/cisplatin +

S1794 gemcitabine, carboplatin + paclitaxel, or carboplatin/cisplatin + pemetrexed with optional pemetrexed maintenance (for those with non-squamous histology). Randomization was stratified by ECOG performance status (0 vs 1), histology (squamous vs nonsquamous), and geographic region (East Asia vs noneEast Asia). Treatment continued until disease progression per RECIST version 1.1, intolerable toxicity, or withdrawal of consent. Patients in the chemotherapy arm who experienced disease progression could cross over to receive pembrolizumab monotherapy. Response was assessed every 9 weeks by blinded independent central review per RECIST version 1.1. The primary endpoint was PFS; secondary endpoints were OS, ORR, and safety. Result: 305 patients were enrolled (pembrolizumab, n¼154; chemotherapy, n¼151). At the time of data cutoff (July 10, 2017) after a median follow-up of 25.2 months, 73 patients (47.4%) in the pembrolizumab arm and 96 patients (63.6%) in the chemotherapy arm had died. The hazard ratio for OS was 0.63 (95% CI, 0.47e0.86; nominal P¼0.002). Median (95% CI) OS was 30.0 (18.3enot reached) months in the pembrolizumab arm and 14.2 (9.8e19.0) months in the chemotherapy arm. The Kaplan-Meier estimate of OS at 12 months was 70.3% (95% CI, 62.3%e76.9%) for the pembrolizumab group and 54.8% (95% CI, 46.4%e62.4%) for the chemotherapy group. 82 patients allocated to the chemotherapy arm crossed over to receive pembrolizumab upon meeting eligibility criteria. Treatment-related adverse events were less frequent in the pembrolizumab arm than in the chemotherapy arm (76.6% versus 90.0%, respectively) as were treatment-related grade 3-5 adverse events (31.2% versus 53.3%). Conclusion: With more than half of patients having OS events and prolonged follow‒up, first-line pembrolizumab monotherapy remains superior to platinum-based chemotherapy despite the crossover from the control arm to an anti-PD1 inhibitor as subsequent therapy. Keywords: KEYNOTE-024, Non-small-cell lung cancer, pembrolizumab

OA 17.07 Long-Term Survival in Atezolizumab-Treated Patients with 2L+ NSCLC from Ph III Randomized OAK Study M. Satouchi,1 L. Fehrenbacher,2 M. Cobo Dols,3 J. Han,4 J. Von Pawel,5 R. Bordoni,6 T. Hida,7 K. Park,8 D. Moro-Sibilot,9 P. Conkling,10 C. Matheny,11 W. Yu,11 P. He,11 M. Kowanetz,11 M. Gandhi,11 M. Ballinger,11 A. Sandler,11 D.R. Gandara12 1Hyogo Cancer Center, Akashi/JP, 2Kaiser Permanente Medical Center, Vallejo/ CA/US, 3Hospital Regional Universitario Carlos Haya, Málaga/ES, 4 National Cancer Center, Goyang/KR, 5Asklepios Fachkliniken MünchenGauting, Gauting/DE, 6Georgia Cancer Specialists and Northside Hospital Cancer Institute, Atlanta/GA/US, 7Aichi Cancer Center Hospital, Nagoya/ JP, 8Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/KR, 9Hôpital Albert Michallon, La Tronche/FR, 10Us Oncology Research, Virginia Oncology Associates, Norfolk/VA/US, 11 Genentech, Inc., South San Francisco/CA/US, 12UC Davis Comprehensive Cancer Center, Sacramento, CA/US Background: Atezolizumab (antiePD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. OAK, a Phase III study of atezolizumab vs docetaxel demonstrated superior OS of atezolizumab. The characteristics of the long-term survivors (LTS) in the OAK primary population (n ¼ 850) are evaluated and describe the largest cohort of cancer immunotherapy-treated NSCLC LTS yet reported. Method: Patients received IV q3w atezolizumab (1200 mg) until PD / loss of clinical benefit or docetaxel (75 mg/m2) until PD / unacceptable toxicity. No crossover was allowed. LTS were defined as patients with OS  24 months and non-LTS as those who died within 24 months of randomization. Patients with OS censored prior to 24 months were not included. Data cutoff, January 23, 2017. Result: A higher 2-year survival rate was observed for the atezolizumab-arm (31%) vs docetaxelarm (21%). After a minimum follow-up of 26 months, there were 119 LTS vs 279 non-LTS in the atezolizumab-arm and 77 LTS vs 299 non-

Journal of Thoracic Oncology

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LTS in the docetaxel-arm. Characteristics of atezolizumab-arm LTS and non-LTS are shown (Table). Atezolizumab-arm LTS were enriched for non-squamous histology and high PD-L1eexpressing tumors, but also included low/no PD-L1eexpressing tumors (40.3%). Atezolizumabarm LTS had higher ORR (39.5%) than non-LTS (5.0%) but included LTS subjects with PD. 52.9% atezolizumab-arm vs 71.4% docetaxelarm LTS received anti-cancer non-protocol therapy (NPT) after discontinuation of protocol-defined therapy. 51.9% of docetaxel-arm LTS vs 12.7% non-LTS received non-protocol immunotherapy. Median treatment exposure in atezolizumab-arm LTS was 18.0 months. Atezolizumab-arm LTS had a comparable safety profile to all atezolizumabtreated population. Conclusion: Atezolizumab provides superior 2year OS benefit vs docetaxel and is well tolerated. The majority of docetaxel-arm LTS received a checkpoint inhibitor as NPT. Atezolizumab LTS appeared to have favorable prognostic factors, including nonsquamous histology, but notably were not limited to patients with RECIST v1.1 response or with PD-L1 expression. Keywords: atezolizumab, advanced NSCLC, cancer immunotherapy

Table. Characteristics of Atezolizumab-Arm Long-Term Survivors (LTS) vs Non-Long Term Survivors (Non-LTS) Atezolizumab LTS Atezolizumab Non-LTS (n [ 119) n (%) (n [ 279) n (%) Sex Male 61 (51.3) Female 58 (48.7) Tobacco use history Never smoker 29 (24.4) Current/previous smoker 90 (75.6) Histology Non-squamous 101 (84.9) Squamous 18 (15.1) No. of prior therapies, 1 89 (74.8) ECOG performance status at baseline 0 60 (50.4) 1 59 (49.6) EGFR mutation status, positive 11 (9.2) PD-L1 IHC subgroup TC3 or IC3 28 (23.5) TC1/2/3 or IC1/2/3 71 (59.7) TC0 and IC0 48 (40.3) Best overall response Complete response 5 (4.2) Partial response 42 (35.3) Stable disease 47 (39.5) Progressive disease 25 (21.0)

183 (65.6) 96 (34.4) 47 (16.8) 232 (83.2) 195 (69.9) 84 (30.1) 209 (74.9) 89 (31.9) 190 (68.1) 26 (9.3) 39 (14.0) 156 (55.9) 119 (42.7) 0 14 97 142

(0) (5.0) (34.8) (50.9)

IC, tumor-infiltrating immune cell; TC, tumor cell. TC3 or IC3 ¼ PD-L1  50% TC or 10% IC; TC1/2/3 or IC1/2/3 ¼ PD-L1  1% on TC or IC; TC0 and IC0 ¼ PDL1 < 1% on TC and IC. NCT02008227.

OA 17.08 Phase II Study of Pembrolizumab for Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Following Completion of Locally Ablative Therapy (LAT) J. Bauml,1 R. Mick,2 C. Ciunci,1 C. Aggarwal,1 T. Evans,1 L. Miller,2 N. Muhammad,2 E. Alley,1 C. Knepley,2 F. Mutale,2 R. Cohen,1 C. Langer1 1Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA/US, 2University of Pennsylvania, Philadelphia, PA/US Background: Patients (pts) with oligometastatic NSCLC may benefit from LAT (e.g., surgery, stereotactic radiation (SRT)). It is unclear if systemic therapy can provide additional benefit after LAT. We are running a Phase II study to evaluate the efficacy of pembrolizumab