title: 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).
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: VU, MF, National Cancer Institute, Santariskiu 1, LT-08660 Vilnius, Lithuania. Electronic address: saulius.cicenas@nvi.lt.
authors.forename: Saulius
authors.initials: S
authors.lastname: Cicènas
authors.affiliation: 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.
authors.forename: Sarayut Lucien
authors.initials: SL
authors.lastname: Geater
authors.affiliation: Complex Oncology Center-Plovdiv, Plovdiv, Bulgaria. Electronic address: petar_petrov_doctor@abv.bg.
authors.forename: Petar
authors.initials: P
authors.lastname: Petrov
authors.affiliation: Uzhgorod Central City Hospital, Hryboiedova St, 20, Uzhgorod, Zakarpats'ka oblast 88000, Ukraine. Electronic address: yhotko@gmail.com.
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Hotko
authors.affiliation: Roche Products Ltd., Hexagon Place, 6 Falcon Way, Welwyn Garden City AL7 1TW, UK. Electronic address: greg.hooper@roche.com.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hooper
authors.affiliation: Roche R&D Center (China) Ltd., 720 Cai Lun Road, Building 5, Shanghai 201203, Pudong, China. Electronic address: fan.xia@roche.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Xia
authors.affiliation: F. Hoffmann-La Roche, Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: nadia.mudie@roche.com.
authors.forename: Nadejda
authors.initials: N
authors.lastname: Mudie
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D000069347:Erlotinib Hydrochloride
keywords: First-line erlotinib; Maintenance erlotinib; Non-small-cell lung cancer; Platinum-based chemotherapy