PMID- 27987585 OWN - NLM STAT- MEDLINE DCOM- 20171218 LR - 20180124 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 102 DP - 2016 Dec TI - Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). PG - 30-37 LID - S0169-5002(16)30504-9 [pii] LID - 10.1016/j.lungcan.2016.10.007 [doi] AB - OBJECTIVE: The phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib at progression in advanced/metastatic non-small-cell lung cancer (NSCLC) that had not progressed following four cycles of platinum-based chemotherapy. MATERIALS AND METHODS: Patients had stage IIIB/IV NSCLC, no known epidermal growth factor receptor (EGFR)-activating mutation, and objective response or disease stabilization after platinum-based induction chemotherapy. Central EGFR-mutation testing was undertaken on tumors from patients with unknown or wild-type EGFR status following local testing. Patients were randomized to receive blinded maintenance erlotinib 150mg/day ('early erlotinib') or placebo. Those who progressed on placebo received open-label erlotinib ('late erlotinib'); patients who progressed on erlotinib received approved second-line chemotherapy or best supportive care. Primary endpoint: overall survival (OS). RESULTS: 643 patients were randomized to receive maintenance erlotinib (n=322) or placebo (n=321). As of March 23, 2015, 242 (75.2%) OS events had occurred with 'early erlotinib' versus 235 (73.2%) with 'late erlotinib'. Median OS was 9.7 and 9.5 months with 'early erlotinib' and 'late erlotinib', respectively (HR, 1.02, 95% CI: 0.85-1.22; log-rank p=0.82). No progression-free survival, objective response rate, or disease control rate benefit was observed with maintenance erlotinib. 410 patients entered the second-line phase of the study: 160 patients (50%) from the maintenance erlotinib arm and 250 patients (78%) from the maintenance placebo arm. The pattern of adverse events (AEs) was consistent with previous trials; 11 patients who received blinded erlotinib and 3 who received placebo died during the blinded maintenance phase due to nontreatment-related AEs. CONCLUSIONS: OS with maintenance erlotinib was not superior to second-line treatment in patients whose tumor did not harbor an EGFR-activating mutation. Safety results were consistent with the established safety profile of erlotinib. Thus, maintenance treatment with erlotinib in patients with advanced/metastatic NSCLC without EGFR-activating mutations is considered unfavorable. CI - Copyright (c) 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. FAU - Cicenas, Saulius AU - Cicenas S AD - VU, MF, National Cancer Institute, Santariskiu 1, LT-08660 Vilnius, Lithuania. Electronic address: saulius.cicenas@nvi.lt. FAU - Geater, Sarayut Lucien AU - Geater SL AD - Division of Respiratory and Respiratory Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Rd., Hat Yai, Songkhla 90110, Thailand. Electronic address: drgeater@gmail.com. FAU - Petrov, Petar AU - Petrov P AD - Complex Oncology Center-Plovdiv, Plovdiv, Bulgaria. Electronic address: petar_petrov_doctor@abv.bg. FAU - Hotko, Yevgeniy AU - Hotko Y AD - Uzhgorod Central City Hospital, Hryboiedova St, 20, Uzhgorod, Zakarpats'ka oblast 88000, Ukraine. Electronic address: yhotko@gmail.com. FAU - Hooper, Gregory AU - Hooper G AD - Roche Products Ltd., Hexagon Place, 6 Falcon Way, Welwyn Garden City AL7 1TW, UK. Electronic address: greg.hooper@roche.com. FAU - Xia, Fan AU - Xia F AD - Roche R&D Center (China) Ltd., 720 Cai Lun Road, Building 5, Shanghai 201203, Pudong, China. Electronic address: fan.xia@roche.com. FAU - Mudie, Nadejda AU - Mudie N AD - F. Hoffmann-La Roche, Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: nadia.mudie@roche.com. FAU - Wu, Yi-Long AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20161020 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Organoplatinum Compounds) RN - DA87705X9K (Erlotinib Hydrochloride) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - Disease Progression MH - Disease-Free Survival MH - Drug Administration Schedule MH - Erlotinib Hydrochloride/*administration & dosage/adverse effects MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/pathology MH - Maintenance Chemotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Organoplatinum Compounds/administration & dosage OTO - NOTNLM OT - First-line erlotinib OT - Maintenance erlotinib OT - Non-small-cell lung cancer OT - Platinum-based chemotherapy EDAT- 2016/12/19 06:00 MHDA- 2017/12/19 06:00 CRDT- 2016/12/19 06:00 PHST- 2016/06/30 00:00 [received] PHST- 2016/10/17 00:00 [revised] PHST- 2016/10/20 00:00 [accepted] PHST- 2016/12/19 06:00 [entrez] PHST- 2016/12/19 06:00 [pubmed] PHST- 2017/12/19 06:00 [medline] AID - S0169-5002(16)30504-9 [pii] AID - 10.1016/j.lungcan.2016.10.007 [doi] PST - ppublish SO - Lung Cancer. 2016 Dec;102:30-37. doi: 10.1016/j.lungcan.2016.10.007. Epub 2016 Oct 20.