title: A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer.
abstract: Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m (2) d1) and either cisplatin (75 mg/m (2) d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed-platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations.
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Jialei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology; Fudan University Shanghai Cancer Center; Shanghai, PR China; Department of Oncology; Shanghai Medical College; Fudan University; Shanghai, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D000077156:Gefitinib; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: D005971:Glutamates; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin; D002945:Cisplatin; D000077156:Gefitinib
keywords: EGFR mutations; gefitinib; non-small cell lung cancer; non-squamous; pemetrexed; phase II randomized trial; platinum
references.citation: J Clin Oncol. 2008 Jan 20;26(3):463-7
references.pmid: 18202421
references.citation: Lung Cancer. 2012 Aug;77(2):339-45
references.pmid: 22494567
references.citation: Eur J Cancer. 2013 Apr;49(6):1205-15
references.pmid: 23477998
references.citation: Expert Opin Pharmacother. 2013 Aug;14(11):1545-58
references.pmid: 23683110
references.citation: Lancet Oncol. 2012 May;13(5):435-6
references.pmid: 22512846
references.citation: Clin Lung Cancer. 2006 May;7(6):385-8
references.pmid: 16800963
references.citation: J Clin Oncol. 2011 Nov 1;29(31):4113-20
references.pmid: 21969500
references.citation: Int J Cancer. 2010 Dec 15;127(12):2893-917
references.pmid: 21351269
references.citation: Lancet Oncol. 2012 May;13(5):466-75
references.pmid: 22512843
references.citation: J Clin Oncol. 2004 Mar 1;22(5):785-94
references.pmid: 14990633
references.citation: J Clin Oncol. 2008 Jul 20;26(21):3543-51
references.pmid: 18506025
references.citation: Lancet Oncol. 2010 Jun;11(6):521-9
references.pmid: 20493771
references.citation: J Clin Oncol. 2004 Mar 1;22(5):777-84
references.pmid: 14990632
references.citation: J Clin Oncol. 2009 Oct 20;27(30):5080-7
references.pmid: 19738125
references.citation: Ann Oncol. 2011 Mar;22(3):559-566
references.pmid: 20702788
references.citation: Ann Oncol. 2013 Sep;24(9):2371-6
references.pmid: 23723294
references.citation: J Clin Oncol. 2009 Jul 1;27(19):3217-24
references.pmid: 19433683
references.citation: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references.pmid: 22237781
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1545-52
references.pmid: 17442998
references.citation: Ann Oncol. 2012 Feb;23(2):388-94
references.pmid: 21610154
references.citation: Lung Cancer. 2012 Aug;77(2):346-52
references.pmid: 22534669
references.citation: Clin Lung Cancer. 2007 Nov;8(9):548-53
references.pmid: 18186959
references.citation: J Clin Oncol. 2005 Sep 1;23(25):5892-9
references.pmid: 16043829
references.citation: Health Technol Assess. 2010 May;14 Suppl 1:47-53
references.pmid: 20507803
references.citation: Eur J Cancer. 2009 Sep;45(13):2298-303
references.pmid: 19473833
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3516-24
references.pmid: 22949150
references.citation: Lancet Oncol. 2013 Jul;14(8):777-86
references.pmid: 23782814
references.citation: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6049-55
references.pmid: 17062680
references.citation: J Surg Oncol. 2013 Feb;107(2):221-6
references.pmid: 22926725