A plain language summary of results from the FLAURA2 study: Effects of initial (first-line) osimertinib plus chemotherapy on the brain in patients with EGFR-mutated advanced non-small cell lung cancer

Plain Language SummaryWhat was the purpose of the FLAURA2 study?This is a summary of results from the FLAURA2 clinical study in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC). The results were published in full in 2023.NSCLC represents 85% of lung cancer cases, but is often not diagnosed until the cancer has spread beyond the lungs, known as 'metastatic' or 'advanced disease'.EGFR('epidermal growth factor receptor') controls how cells grow and divide.Changes (mutations) in the EGFR gene alter the EGFR-receptor, transforming healthy cells into cancer cells, as occurs in EGFR-mutated NSCLC.Osimertinib (TAGRISSO®) is a drug that has already been shown to treat EGFR-mutated NSCLC by blocking the effects of mutated EGFR, and preventing, slowing or stopping the growth of cancer cells. Osimertinib is approved and recommended by international treatment guidelines as initial (first-line) treatment for EGFR-mutated advanced NSCLC.EGFR-mutated NSCLC is particularly prone to spreading to the brain or spinal cord (known as central nervous system [CNS] metastases). The FLAURA2 study assessed if adding chemotherapy to osimertinib treatment could improve outcomes for patients, compared to osimertinib alone. Patients with brain metastases could participate as long as they were asymptomatic (not experiencing symptoms because of the brain metastases) or the brain metastases had been treated and were stable (not increasing in size or getting worse).The primary findings of FLAURA2 were that osimertinib plus chemotherapy extended the time before NSCLC tumor growth/spread, or patient death compared to osimertinib alone.What were the results in patients with and without brain metastases?In patients with brain metastases before treatment, those who were treated with osimertinib plus chemotherapy had a lower risk of their brain tumors growing/spreading, or death compared with patients who received osimertinib alone. Of those without brain metastases before treatment, very few in either treatment group developed a brain metastasis during the study.What do the results of the study mean?Based on the primary results of FLAURA2, osimertinib plus chemotherapy was approved for first-line treatment of EGFR-mutated advanced NSCLC. At the time of publication the FLAURA2 study is ongoing; more results, including survival rates, are expected to be released in the future.This is an abstract of the Plain Language Summary of Publication article.View the full Plain Language Summary PDF of this article to read the full-text AcknowledgmentsThe authors and AstraZeneca would like to thank all the patients who participated in this study, their families and all of the study center staff members who contributed. The authors would like to acknowledge the contributions of the late Dr Libor Havel (Charles University, Thomayer University Hospital, Prague, Czech Republic) to the FLAURA2 study. Dr Havel was a co-author of the FLAURA2 manuscript published in the Journal of Clinical Oncology. The authors would also like to thank Nicoline Ehrhardt, Laura Floyd, and Dave Nitsche for reviewing this article and providing valuable contributions to the development of this plain language summary publication.Disclosure statementDisclosure forms provided by the authors are available with the full text of the original article at https://ascopubs.org/doi/pdf/10.1200/JCO.23.02219. Pasi A. Jänne reports consulting fees from AbbVie, Accutar Biotech, Allorion Therapeutics, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Duality Biologics, Eli Lilly, Eisai, F. Hoffmann-La Roche, Frontier Medicines, Hongyun Biotechnology, Merus, Mirati Therapeutics, Novartis, Nuvalent, Pfizer, Sanofi Pasteur Biologics LLC, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, Takeda, Transcenta, and Voronoi; stock with Gatekeeper Pharmaceuticals; patent/inventor with Laboratory corporation. David Planchard reports consulting fees from AbbVie, Arrivent, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Daiichi Sankyo, F. Hoffmann-La Roche, Janssen, Merck, Mirati Therapeutics, Novartis, Pfizer, Pierre Fabre Pharmaceuticals, Inc, Samsung, Sanofi-Aventis U.S. LLC, Seagen Inc, Taiho Pharmaceutical, and Takeda. Kunihiko Kobayashi reports speaker fees from AstraZeneca; consulting fees from Daiichi Sankyo/UCB Japan; research funding from Zeria Pharmaceutical Co; co-inventor on Japanese patent # 7422498. Ying Cheng has nothing to disclose. Chee Khoon Lee reports grants from Amgen, AstraZeneca, Merck kGA, and Roche; honoraria/lecture/speaker fees from Amgen, AstraZeneca, Gilead, GSK, Janssen, Merck kGA, Merck, Novartis, Roche, and Takeda.Natalia Valdiviezo has nothing to disclose. Konstantin Laktionov has nothing to disclose. Tsung-Ying Yang reports consulting/advisory roles with AstraZeneca and Takeda. Yan Yu has nothing to disclose. Terufumi Kato reports employment with Lilly; honoraria from Chugai Pharma, Ono Pharmaceutical, Lilly, AstraZeneca, Taiho Pharmaceutical, Pfizer, MSD, Novartis, Daiichi Sankyo, GlaxoSmithKline, Amgen, Merck KGaA, Takeda, BeiGene, Boehringer Ingelheim, Janssen, Bristol Myers Squibb Japan, and Roche; consulting/advisory roles with AstraZeneca, MSD, Pfizer, BeiGene, Novartis, Daiichi Sankyo, Janssen, Merck KGaA, Amgen; research funding from Chugai Pharma, MSD, Pfizer, AstraZeneca, Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck KGaA, Takeda, Haihe Biopharma, Blueprint Medicines, Turning Point Therapeutics, Daiichi Sankyo, BeiGene, Gilead Sciences, Bayer, GlaxoSmithKline, and Janssen. Liyan Jiang has nothing to disclose. Busyamas Chewaskulyong reports honoraria from Amgen, AstraZeneca, Eisai, Novartis, Roche, and Zuellig Pharma; consulting/advisory roles with Amgen, AstraZeneca, Eisai, MSD Oncology, Novartis, Pfizer, Pharma, Roche, and Zuellig; speakers' bureau from AstraZeneca, Bristol Myers Squibb, Eisai, MSD Oncology, Novartis, Pfizer, Roche, and Zuellig Pharma;research funding from AstraZeneca, and roche; travel/accommodation/expenses from Eisai, MSD Oncology, and Zuellig Pharma. Sarayut Lucien Geater reports advisory board fees from Boehringer Ingelheim, and Pfizer; principal investigator for AstraZeneca, Boehringer Ingelheim, F. Hoffman-La Roche, MSD, and Novartis.Jean-Marc Maurel has nothing to disclose. Carlos Rojas reports consulting/advisory role with AstraZeneca, Bristol Myers Squibb, Knight Therapeutics/Biotoscana, MSD, Pfizer, and Roche; research funding from AstraZeneca, Bristol Myers Squibb/Celgene, Knight Therapeutics/Biotoscana, Merck, Pfizer, and Roche; expert testimony with AstraZeneca, Bristol Myers Squibb, and Roche; travel, accommodations, expenses from Bristol Myers Squibb. Toshiaki Takahashi reports honoraria from Amgen, AstraZeneca Japan, Bristol Myers Squibb Japan, Chugai Pharma, Lilly Japan, MSD K.K, Novartis, Ono Pharmaceutical, Pfizer, and Takeda; research funding from Amgen, AnHeart Therapeutics Inc, AstraZeneca Japan, Chugai Pharma, Janssen, Lilly Japan, Merck, MSD K.K, and Pfizer. Frances A. Shepherd reports stock with AstraZeneca, and Lilly; honoraria from AstraZeneca, Daiichi Sankyo, Merck Serono, and Takeda; consulting/advisory roles with AstraZeneca, and Merck Serono; research funding from AstraZeneca/MedImmune, Bristol Myers Squibb, Lilly, Pfizer, and Roche Canada. Kentaro Tanaka reports honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo/UCB Japan, Lilly Japan, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche, and Takeda; consulting or advisory role from Janssen; research funding from AstraZeneca/MedImmune, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo/UCB Japan, GlaxoSmithKline, and MSD. Dana Ghiorghiu reports employment and stock with AstraZeneca. Neha P. Amin reports employment and stock with AstraZeneca; travel, accommodations, expenses with AstraZeneca. Elena Armenteros-Monterroso reports employment and stock with AstraZeneca. Xiangning Huang reports employment and stock with AstraZeneca. Ammar Ahmed Chaudhry reports employment and stock with AstraZeneca; travel, accommodations, expenses with AstraZeneca. James Chih-Hsin Yang reports advisory board fees from Amgen, AstraZeneca, AbbVie, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Gilead, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron Pharmaceuticals, Takeda, Yuhan Pharmaceuticals, GlaxoSmithkline, ArriVent, AnHeart Therapeutics, and Black Diamond Therapeutics Inc; coordinating PI for AstraZeneca, Dizal Pharmaceuticals, and MSD; travel funding from AstraZeneca, Dizal Pharmaceuticals, and Takeda Oncology; local PI from Amgen, ArriVent, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Dizal Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche, Gilead, Ipsen, Janssen, Merck KGaA, MSD, Novartis, Numab Therapeutics AG, Takeda, and Yuhan Pharmaceuticals; member of ASCO, ESMO, IASLC; research grants from AstraZeneca, and F. Hoffmann-La Roche; steering committee member for Amgen, ArriVent, AstraZeneca, Bayer, Black Diamond Therapeutics Inc., Daiichi Sankyo, Dizal Pharmaceuticals, Eli Lilly, Janssen, Merck KGaA, MSD, Numab Therapeutics AG, Takeda, and Yuhan Pharmaceuticals.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Medical writing support under the direction of the authors was provided by Alice Walter, BSc, of Ashfield MedComms, an Inizio company, funded by AstraZeneca in accordance with Good Publications Practice (GPP) guidelines (https://www.ismpp.org/gpp-2022).Patient reviewers on this PLSP have received honorarium from Future Oncology for their review work but have no other relevant financial relationships to disclose.Ethical disclosureThe trial was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines (as defined by the International Conference for Harmonisation), applicable regulatory requirements, and the policy of the trial sponsor, AstraZeneca, on bioethics and human biologic samples. All the patients provided written informed consent.FundingThe pharmaceutical company AstraZeneca funded and were responsible for conducting this study.