Lung Cancer—Non-Small Cell Metastatic
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LUNG CANCER—NON-SMALL CELL METASTATIC 9500 Oral Abstract Session, Fri, 8:00 AM-11:00 AM Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. Suresh S. Ramalingam, Tudor Eliade Ciuleanu, Adam Pluzanski, Jong-Seok Lee, Michael Schenker, Reyes Bernabe Caro, Ki Hyeong Lee, Bogdan Zurawski, Clarisse Audigier-Valette, Mariano Provencio, Helena Linardou, Sang-We Kim, Hossein Borghaei, Matthew David Hellmann, Kenneth John O’Byrne, Luis G. Paz-Ares, Martin Reck, Faith Ellen Nathan, Julie R. Brahmer; Winship Cancer Institute, Emory University, Atlanta, GA; Institutul oncologic Orif Dr Ion Chiricuta and UNF Iulia Hatieganu, Cluj Napoca, Romania; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Seoul National University Bundang Hospital, Seongnam, South Korea; SF. Nectarie Oncology Center, Craiova, Romania; Hospital Universitario Virgen Del Rocio, Seville, Spain; Chungbuk National Uni- versity Hospital, Cheongju, Chungbuk, South Korea; Ambulatorium Chemioterapii, Bydgoszcz, Poland; Hopitalˆ Sainte Musse, Toulon, France; Hosp. Univ. Puerta de Hierro, Madrid, Spain; Metropolitan Hospital, Athens, Greece; Asan Medical Center, Seoul, Korea, Republic of (South); Fox Chase Cancer Center, Philadelphia, PA; Memorial Sloan Kettering Cancer Center, New York, NY; Princess Alexandra Hospital, Brisbane, Australia; Hospital Universitario 12 de Octubre, CNIO, Universidad Complutense & CiberOnc, Madrid, Spain; Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; Bristol-Myers Squibb, Princeton, NJ; Sidney Kimmel Com- prehensive Cancer Center at Johns Hopkins, Baltimore, MD Background: In the phase 3 CheckMate 227 Part 1 (NCT02477826; minimum follow-up, 29.3 mo), 1L NIVO + IPI significantly improved overall survival (OS) vs chemo in treatment-naive patients (pts) with aNSCLC and tumor PD-L1 expression $ 1% (primary analysis) or , 1% (pre-specified descriptive analysis). Here we report data with 3-y minimum follow-up. Methods: Pts with stage IV / recurrent NSCLC and PD-L1 $ 1% (n = 1189) were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W) alone, or chemo. Pts with PD-L1 , 1% (n = 550) were randomized to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Primary endpoint was OS with NIVO + IPI vs chemo in pts with PD-L1 $ 1%. An exploratory analysis of OS in pts by response status (CR/PR, SD, progressive disease [PD]) at 6 mo was conducted. Results: After a median follow-up of 43.1 mo (database lock, 28 Feb 2020), pts with PD-L1 $ 1% continued to derive OS benefit from NIVO + IPI vs chemo (HR: 0.79; 95% CI, 0.67–0.93); 3-y OS rates were 33% (NIVO + IPI), 29% (NIVO), and 22% (chemo). At 3 y, 18% of pts with PD-L1 $ 1% treated with NIVO + IPI remained progression-free vs 12% with NIVO and 4% with chemo; 38% of confirmed responders remained in response in the NIVO + IPI arm at 3 y vs 32% in the NIVO arm and 4% in the chemo arm. In pts with PD-L1 , 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 3-y OS rates were 34% (NIVO + IPI), 20% (NIVO + chemo), and 15% (chemo); 13%, 8%, and 2% of pts remained progression-free; and 34%, 15%, and 0% of confirmed responders remained in response, respectively. Pts with PD-L1 $ 1% with either CR/PR at 6 mo had longer subsequent OS with NIVO + IPI vs chemo; pts with SD or PD at 6 mo had generally similar subsequent OS between treatments (Table); results in PD-L1 , 1% pts will be presented. Any-grade / grade 3–4 treatment-related AEs were observed in 77% / 33% of all pts treated with NIVO + IPI, and 82% / 36% with chemo. Conclusions: With 3 y minimum follow-up, NIVO + IPI continued to provide durable and long-term OS benefits vs chemo for pts in 1L aNSCLC. Pts with PD-L1 $ 1% who achieved CR/PR at 6 mo had marked OS benefit with NIVO + IPI vs chemo. No new safety signals were identified for NIVO + IPI. Clinical trial information: NCT02477826. Research Sponsor: Bristol-Myers Squibb and Ono Pharmaceutical. Landmark analysis of OS by response status at 6 mo in pts with PD-L1 $ 1% (NIVO + IPI vs chemo). Response status at Post-landmark Post-landmark Post-landmark Pts alive at 6 mo 6 mo, % 1-y OS rate, % 2-y OS rate, % 3-y OS rate, % NIVO + IPI CR or PR, 39 vs 25 90 vs 73 76 vs 51 70 vs 39 (n = 295) vs SD, 14 vs 18 69 vs 54 45 vs 38 34 vs 33 Chemo PD, 46 vs 58 44 vs 47 22 vs 25 19 vs 17 (n = 306) © 2020 American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. LUNG CANCER—NON-SMALL CELL METASTATIC 9501 Oral Abstract Session, Fri, 8:00 AM-11:00 AM Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. Martin Reck, Tudor-Eliade Ciuleanu, Manuel Cobo Dols, Michael Schenker, Bogdan Zurawski, Juliana Menezes, Eduardo Richardet, Jaafar Bennouna, Enriqueta Felip, Oscar Juan-Vidal, Aurella Alexandru, Hiroshi Sakai, Arnaud Scherpereel, Shun Lu, Thomas John, David Paul Carbone, Stephanie Meadows-Shropshire, Jinchun Yan, Luis G. Paz-Ares; Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany; Institutul Oncologic Prof. Dr. Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania; Hospital Carlos Haya de M´alaga, Malaga, ´ Spain; SF. Nectarie Oncology Center, Craiova, Romania; Ambulatorium Chemioterapii, Bydgoszcz, Poland; Hospital Nossa Senhora Da Conceiç~ao, Porto Alegre, Brazil; Instituto Oncologico de C´ordoba, C´ordoba, Argentina; Thoracic Oncology Unit, University Hospital of Nantes, Nantes, France; Vall d’Hebron University Hospital, Barcelona, Spain; Hospital Universitario y Politecnico ´ La Fe, Valencia, Spain; Institute of Oncology "Prof. Dr. Alexandru Trestioreanu" Bucha, Bucharest, Romania; Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan; Regional University Hospital Center of Lille, Hospital Calmette, Lille, France; Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Austin Hospital, Victoria, Australia; The Ohio State University Com- prehensive Cancer Center, Columbus, OH; Bristol-Myers Squibb, Princeton, NJ; Hospital Universitario 12 de Octubre, CNIO, Universidad Complutense & CiberOnc, Madrid, Spain Background: NIVO + IPI was shown to improve overall survival (OS) and durability of response vs chemo in 1L advanced NSCLC in CheckMate 227 Part 1, regardless of PD-L1 expression. We hypothesized that a limited course of chemo combined with NIVO + IPI could provide rapid disease control while building on the durable OS benefit seen with dual PD-1 and CTLA-4 inhibition. CheckMate 9LA (NCT03215706) is a phase 3 randomized study evaluating NIVO + IPI + 2 cycles chemo vs chemo in 1L stage IV/recurrent NSCLC. Methods: Adults with tx-naive, histologically confirmed stage IV/recurrent NSCLC, ECOG performance status 0–1, and no known sensitizing EGFR/ALK alterations were ran- domized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles) (n = 361) or chemo (4 cycles) alone (n = 358), stratified by PD-L1 (, 1% vs $ 1%), sex, and histology (squamous vs non-squamous). Chemo was based on histology. Pts with non-squamous NSCLC in the chemo-only arm could receive optional pemetrexed maintenance. Pts were treated with immunotherapy until disease progression, unacceptable toxicity, or for 2 y. The primary endpoint was OS; the interim analysis using Lan–DeMets alpha spending function with O’Brien–Fleming boundary was planned at ~80% information fraction (ie, after observing ~322 total events). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by blinded independent central review, and efficacy by PD-L1 subgroups. Exploratory endpoints included safety/tolerability. Results: Baseline characteristics were balanced across arms. At a preplanned interim analysis (minimum follow-up 8.1 mo), OS was significantly prolonged with NIVO + IPI + chemo vs chemo (HR 0.69, 96.71% CI: 0.55–0.87; P = 0.0006); statistically significant improvements in PFS and ORR were seen. With longer follow-up (minimum 12.7 mo), NIVO + IPI + chemo vs chemo continued to provide longer OS; median 15.6 vs 10.9 mo (HR 0.66, 95% CI: 0.55–0.80); 1-y OS rates were 63 vs 47%. Clinical benefit was consistent across all efficacy measures in key subgroups including by PD-L1 and histology. Grade 3–4 tx-related adverse events were reported in 47 vs 38% of pts in the NIVO + IPI + chemo vs chemo arms, respectively. Conclusions: CheckMate 9LA met its primary endpoint: a statistically significant im- provement in OS was observed with NIVO + NSCLC-optimized IPI + a limited course of chemo vs chemo (4 cycles) in 1L advanced NSCLC. No new safety signals were reported. Clinical trial information: NCT03215706. Research Sponsor: Bristol-Myers Squibb and Ono Pharmaceutical. © 2020 American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. LUNG CANCER—NON-SMALL CELL METASTATIC 9502 Oral Abstract Session, Fri, 8:00 AM-11:00 AM CCTG BR.34: A randomized trial of durvalumab and tremelimumab +/- platinum-based chemotherapy in patients with metastatic (Stage IV) squamous or nonsquamous non-small cell lung cancer (NSCLC). Natasha B. Leighl, Scott Andrew Laurie, Glenwood D. Goss, Brett Gordon Maxwell