title: Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.
abstract: The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71-0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14-1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90-1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3-4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Tianjin Third Central Hospital, Tianjin, 300170, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Heilongjiang Provincial Hospital, Harbin, 150000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Maopeng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009154:Mutation; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors
keywords: epidermal growth factor receptor; non-small cell lung cancer; overall survival; tyrosine kinase inhibitor