Journal ArticleDOI
Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial.
Kazuhiko Nakagawa,Edward B Garon,Takashi Seto,Makoto Nishio,Santiago Ponce Aix,Luis Paz-Ares,Chao-Hua Chiu,Keunchil Park,Silvia Novello,Ernest Nadal,Fumio Imamura,Kiyotaka Yoh,Jin-Yuan Shih,Kwok Hung Au,Denis Moro-Sibilot,Sotaro Enatsu,Annamaria Zimmermann,Bente Frimodt-Moller,Carla Visseren-Grul,Martin Reck,Quincy Chu,Alexis B. Cortot,Jean-Louis Pujol,Elizabeth Fabre,Corinne Lamour,Helge Bischoff,Jens Kollmeier,M Kimmich,Walburga Engel-Riedel,Stefan Hammerschmidt,Wolfgang Schütte,Konstantinos N. Syrigos,James Chung-Man Ho,Kwok-Hung Au,Andrea Ardizzoni,Giulia Pasello,Vanessa Gregorc,Alessandro Del Conte,Domenico Galetta,Toshiaki Takahashi,Toru Kumagai,Katsuyuki Hotta,Yasushi Goto,Yukio Hosomi,Hiroshi Sakai,Yuichi Takiguchi,Young Hak Kim,Takayasu Kurata,Hiroyuki Yamaguchi,Haruko Daga,Isamu Okamoto,Miyako Satouchi,Satoshi Ikeda,Kazuo Kasahara,Shinji Atagi,Koichi Azuma,Keisuke Aoe,Yoshitsugu Horio,Nobuyuki Yamamoto,Hiroshi Tanaka,Satoshi Watanabe,Naoyuki Nogami,Tomohiro Ozaki,Ryo Koyama,Tomonori Hirashima,Hiroyasu Kaneda,Keisuke Tomii,Yuka Fujita,Masahiro Seike,Naoki Nishimura,Terufumi Kato,Masao Ichiki,Hideo Saka,Katsuya Hirano,Yasuharu Nakahara,Shunichi Sugawara,Sang-We Kim,Young Joo Min,Hyun Woo Lee,Jin-Hyoung Kang,Ho Jung An,Ki Hyeong Lee,Jin Soo Kim,Gyeong-Won Lee,Sung Yong Lee,A. Alexandru,Anghel Adrian Udrea,Óscar Juan-Vidal,Ernest Nadal-Alforja,Ignacio Gil-Bazo,Santiago Ponce-Aix,Belén Rubio-Viqueira,Miriam Alonso Garcia,Enriqueta Felip Font,Jose Fuentes Pradera,Juan Coves Sarto,Meng-Chih Lin,Wu Chou Su,Te Chun Hsia,Gee-Chen Chang,Yu-Feng Wei,Jian Su,Irfan Cicin,Tuncay Göksel,Hakan Harputluoglu,Ozgur Ozyilkan,Ivo Henning,Sanjay Popat,Olivia Hatcher,Kathryn Mileham,Jared Acoba,Edward B. Garon,Gabriel Jung,Moses Sundar Raj,William J. Martin,Shaker R. Dakhil +115 more
TLDR
The RELAY trial as mentioned in this paper evaluated erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC.Abstract:
Summary Background Dual blockade of the EGFR and VEGF pathways in EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC. Methods This is a worldwide, double-blind, phase 3 trial done in 100 hospitals, clinics, and medical centres in 13 countries. Eligible patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no CNS metastases. We randomly assigned eligible patients in a 1:1 ratio to receive oral erlotinib (150 mg/day) plus either intravenous ramucirumab (10 mg/kg) or matching placebo once every 2 weeks. Randomisation was done by an interactive web response system with a computer-generated sequence and stratified by sex, geographical region, EGFR mutation type, and EGFR testing method. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov, NCT02411448, and is ongoing for long-term survival follow-up. Findings Between Jan 28, 2016, and Feb 1, 2018, 449 eligible patients were enrolled and randomly assigned to treatment with ramucirumab plus erlotinib (n=224) or placebo plus erlotinib (n=225). Median duration of follow-up was 20·7 months (IQR 15·8–27·2). At the time of primary analysis, progression-free survival was significantly longer in the ramucirumab plus erlotinib group (19·4 months [95% CI 15·4–21·6]) than in the placebo plus erlotinib group (12·4 months [11·0–13·5]), with a stratified hazard ratio of 0·59 (95% CI 0·46–0·76; p Interpretation Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC. Safety was consistent with the safety profiles of the individual compounds in advanced lung cancer. The RELAY regimen is a viable new treatment option for the initial treatment of EGFR-mutated metastatic NSCLC. Funding Eli Lilly.read more
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Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update
Nasser H. Hanna,Bryan J. Schneider,Sarah Temin,Sherman Baker,Julie R. Brahmer,Peter M. Ellis,Laurie E. Gaspar,Laurie E. Gaspar,Rami Y. Haddad,Paul J. Hesketh,Dharamvir Jain,Ishmael Jaiyesimi,David H. Johnson,Natasha B. Leighl,Tanyanika Phillips,Gregory J. Riely,Andrew G. Robinson,Rafael Rosell,Joan H. Schiller,Navneet Singh,David R. Spigel,Janis O. Stabler,Joan Tashbar,Gregory A. Masters +23 more
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Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.
David S. Ettinger,Douglas E. Wood,Dara L. Aisner,Wallace Akerley,Jessica Bauman,Ankit Bharat,Debora S. Bruno,Joe Y. Chang,Lucian R. Chirieac,Thomas A. D'Amico,Malcolm M. DeCamp,Thomas J. Dilling,Jonathan E. Dowell,Scott N. Gettinger,Travis E. Grotz,Matthew A. Gubens,Aparna Hegde,Rudy P. Lackner,Michael Lanuti,Jules Lin,Billy W. Loo,Christine M. Lovly,Fabien Maldonado,Erminia Massarelli,Daniel Morgensztern,Thomas Ng,Gregory A. Otterson,Jose M. Pacheco,Sandip Pravin Patel,Gregory J. Riely,Jonathan W. Riess,Steven E. Schild,Theresa A. Shapiro,Aditi P. Singh,James P. Stevenson,Alda L. Tam,Tawee Tanvetyanon,Jane Yanagawa,Stephen C. Yang,Edwin Yau,Kristina M. Gregory,Miranda Hughes +41 more
TL;DR: Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer, and this selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastasis NSLI and actionable mutations.
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Correction to: "Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up".
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TL;DR: Department of Medical Oncology, Thoracic Group, Gustave-Roussy Villejuif, France; Royal Marsden Hospital, London; Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, UK; Department of Oncologists, University of Turin, San Luigi Hospital, Orbassano, Italy.
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Update 2020: Management of Non-Small Cell Lung Cancer.
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Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer
Jean-Charles Soria,Yuichiro Ohe,Johan Vansteenkiste,Thanyanan Reungwetwattana,Busyamas Chewaskulyong,Ki Hyeong Lee,Arunee Dechaphunkul,Fumio Imamura,Naoyuki Nogami,Takayasu Kurata,Isamu Okamoto,Caicun Zhou,Byoung Chul Cho,Ying Cheng,Eun Kyung Cho,Pei Jye Voon,David Planchard,Wu Chou Su,Jhanelle E. Gray,Siow-Ming Lee,Rachel Hodge,Marcelo Marotti,Yuri Rukazenkov,Suresh S. Ramalingam +23 more
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Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †
Silvia Novello,Fabrice Barlesi,Raffaele Califano,Raffaele Califano,Tanja Cufer,Simon Ekman,M. Giaj Levra,Keith M. Kerr,Sanjay Popat,Martin Reck,Suresh Senan,G Simo,Johan Vansteenkiste,Sanne Peters +13 more
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Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancers
Helena A. Yu,Maria E. Arcila,Natasha Rekhtman,Camelia S. Sima,Maureen F. Zakowski,William Pao,Mark G. Kris,Vincent A. Miller,Marc Ladanyi,Gregory J. Riely +9 more
TL;DR: This is the largest series reporting mechanisms of acquired resistance to EGFR-TKI therapy and identifies EGFR T790M as the most common mechanism of acquired Resistance, whereas MET amplification, HER2 amplification, and small cell histologic transformation occur less frequently.
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Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial
Keunchil Park,Eng Huat Tan,Kenneth J. O'Byrne,Li Zhang,Michael Boyer,Tony Mok,Vera Hirsh,James Chih-Hsin Yang,Ki Hyeong Lee,Shun Lu,Yuankai Shi,Sang We Kim,Janessa Laskin,Dong Wan Kim,Catherine Dubos Arvis,Karl Kölbeck,Scott A. Laurie,Chun-Ming Tsai,Mehdi Shahidi,MI-Young Kim,Dan Massey,V. Zazulina,Luis Paz-Ares +22 more
TL;DR: Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile.
Journal ArticleDOI
Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial.
Yi-Long Wu,Ying Cheng,Xiangdong Zhou,Ki Hyeong Lee,Kazuhiko Nakagawa,Seiji Niho,Fumito Tsuji,R. Linke,Rafael Rosell,Jesus Corral,Maria Rita Migliorino,Adam Pluzanski,Eric Sbar,Tao Wang,Jane Liang White,Sashi Nadanaciva,Rickard Sandin,Tony Mok +17 more
TL;DR: Dacomit inib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population.
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