Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

• Published in: PloS one Vol. 10; no. 7; p. e0131278
• Main Authors: Xu, J L, Jin, B, Ren, Z H, Lou, Y Q, Zhou, Z R, Yang, Q Z, Han, B H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.07.2015; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bias; Cancer; Cancer therapies; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; Cisplatin - administration & dosage; Clinical trials; Combinatorial analysis; Cytotoxicity; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease-Free Survival; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - adverse effects; Ethnicity; Female; Gemcitabine; Humans; Inhibitor drugs; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Medical prognosis; Meta-analysis; Middle Aged; Multicenter Studies as Topic - statistics & numerical data; Mutation; Neoplasm Proteins - antagonists & inhibitors; Non-small cell lung carcinoma; Paclitaxel - administration & dosage; Patients; Pemetrexed - administration & dosage; Protein Kinase Inhibitors - administration & dosage; Publication Bias; Randomized Controlled Trials as Topic - statistics & numerical data; Smoking; Smoking - epidemiology; Statistical analysis; Statistical significance; Studies; Systematic review; Treatment Outcome; Tumors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131278

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. EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015). 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). 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.