PMID- 28958502 OWN - NLM STAT- MEDLINE DCOM- 20171215 LR - 20220410 IS - 1474-5488 (Electronic) IS - 1470-2045 (Linking) VI - 18 IP - 11 DP - 2017 Nov TI - 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. PG - 1454-1466 LID - S1470-2045(17)30608-3 [pii] LID - 10.1016/S1470-2045(17)30608-3 [doi] AB - BACKGROUND: Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC). METHODS: In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged >/=18 years or >/=20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions. We randomly assigned participants (1:1) to receive oral dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or another discontinuation criterion was met. Randomisation, stratified by race and EGFR mutation type, was done with a computer-generated random code assigned by a central interactive web response system. The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01774721, and is ongoing but no longer recruiting patients. FINDINGS: Between May 9, 2013, and March 20, 2015, 452 eligible patients were randomly assigned to receive dacomitinib (n=227) or gefitinib (n=225). Median duration of follow-up for progression-free survival was 22.1 months (95% CI 20.3-23.9). Median progression-free survival according to masked independent review was 14.7 months (95% CI 11.1-16.6) in the dacomitinib group and 9.2 months (9.1-11.0) in the gefitinib group (hazard ratio 0.59, 95% CI 0.47-0.74; p<0.0001). The most common grade 3-4 adverse events were dermatitis acneiform (31 [14%] of 227 patients given dacomitinib vs none of 224 patients given gefitinib), diarrhoea (19 [8%] vs two [1%]), and raised alanine aminotransferase levels (two [1%] vs 19 [8%]). Treatment-related serious adverse events were reported in 21 (9%) patients given dacomitinib and in ten (4%) patients given gefitinib. Two treatment-related deaths occurred in the dacomitinib group (one related to untreated diarrhoea and one to untreated cholelithases/liver disease) and one in the gefitinib group (related to sigmoid colon diverticulitis/rupture complicated by pneumonia). INTERPRETATION: Dacomitinib 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. FUNDING: SFJ Pharmaceuticals Group and Pfizer. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Wu, Yi-Long AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn. FAU - Cheng, Ying AU - Cheng Y AD - Jilin Provincial Cancer Hospital, Changchun, China. FAU - Zhou, Xiangdong AU - Zhou X AD - First Affiliated Hospital of Third Military Medical University, Chongqing, China. FAU - Lee, Ki Hyeong AU - Lee KH AD - Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea. FAU - Nakagawa, Kazuhiko AU - Nakagawa K AD - Kindai University Hospital, Osaka, Japan. FAU - Niho, Seiji AU - Niho S AD - National Cancer Center Hospital East, Kashiwa, Japan. FAU - Tsuji, Fumito AU - Tsuji F AD - SFJ Pharma Japan, Osaka, Japan. FAU - Linke, Rolf AU - Linke R AD - SFJ Pharmaceuticals Group, Pleasanton, CA, USA. FAU - Rosell, Rafael AU - Rosell R AD - Catalan Institute of Oncology, Barcelona, Spain. FAU - Corral, Jesus AU - Corral J AD - Hospital Universitario Virgen del Rocio, Seville, Spain. FAU - Migliorino, Maria Rita AU - Migliorino MR AD - Pulmonary Oncology Unit, San Camillo-Forlanini Hospital, Rome, Italy. FAU - Pluzanski, Adam AU - Pluzanski A AD - The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland. FAU - Sbar, Eric I AU - Sbar EI AD - Pfizer, Collegeville, PA, USA. FAU - Wang, Tao AU - Wang T AD - Pfizer, Groton, CT, USA. FAU - White, Jane Liang AU - White JL AD - Pfizer, Groton, CT, USA. FAU - Nadanaciva, Sashi AU - Nadanaciva S AD - Pfizer, Groton, CT, USA. FAU - Sandin, Rickard AU - Sandin R AD - Pfizer, Sollentuna, Sweden. FAU - Mok, Tony S AU - Mok TS AD - State Key Laboratory of South China, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China. LA - eng SI - ClinicalTrials.gov/NCT01774721 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20170925 PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 RN - 0 (Quinazolines) RN - 0 (Quinazolinones) RN - 5092U85G58 (dacomitinib) RN - S65743JHBS (Gefitinib) SB - IM CIN - Lancet Oncol. 2017 Nov;18(11):1425-1426. PMID: 28958503 CIN - Lancet Oncol. 2018 Jan;19(1):e4. PMID: 29304361 CIN - Lancet Oncol. 2018 Jan;19(1):e5. PMID: 29304363 CIN - Transl Lung Cancer Res. 2018 Apr;7(Suppl 2):S100-S102. PMID: 29780702 CIN - Transl Lung Cancer Res. 2018 Apr;7(Suppl 2):S134-S137. PMID: 29780706 MH - Adult MH - Aged MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/*mortality MH - Confidence Intervals MH - Disease-Free Survival MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Female MH - Gefitinib MH - Genes, erbB-1/*drug effects/genetics MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/genetics/mortality MH - Male MH - Maximum Tolerated Dose MH - Middle Aged MH - Mutation MH - Prognosis MH - Quinazolines/adverse effects/*therapeutic use MH - Quinazolinones/adverse effects/*therapeutic use MH - Survival Analysis MH - Treatment Outcome EDAT- 2017/09/30 06:00 MHDA- 2017/12/16 06:00 CRDT- 2017/09/30 06:00 PHST- 2017/05/30 00:00 [received] PHST- 2017/07/20 00:00 [revised] PHST- 2017/07/24 00:00 [accepted] PHST- 2017/09/30 06:00 [pubmed] PHST- 2017/12/16 06:00 [medline] PHST- 2017/09/30 06:00 [entrez] AID - S1470-2045(17)30608-3 [pii] AID - 10.1016/S1470-2045(17)30608-3 [doi] PST - ppublish SO - Lancet Oncol. 2017 Nov;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3. Epub 2017 Sep 25.