title: Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis.
abstract: BACKGROUND
  Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC.
  
  
  METHODS
  EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015).
  
  
  RESULTS
  Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06).
  
  
  CONCLUSIONS
  Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation-positive disease. In addition, intercalated administration is an effective combinatorial strategy.
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Xu
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: B
authors.initials: B
authors.lastname: Jin
authors.affiliation: The Ninth People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Ren
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Lou
authors.affiliation: Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, China.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Zhou
authors.affiliation: Department of Gynecology, Women and Child Care of Heyuan, Guangdong, China.
authors.forename: Q Z
authors.initials: QZ
authors.lastname: Yang
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: B H
authors.initials: BH
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D000068437:Pemetrexed; D003841:Deoxycytidine; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine