Pemetrexed/carboplatin plus gefitinib as a first-line treatment for EGFR-mutant advanced nonsmall cell lung cancer: a Bayesian network meta-analysis

Abstract

Background: First-line treatments for nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations have been evaluated in various clinical trials. However, it remains unclear which is the optimal treatment. Methods: A Bayesian network meta-analysis was used to assess the efficacy and safety profile of gefitinib, erlotinib, afatinib, dacomitinib, osimertinib, erlotinib plus bevacizumab and pemetrexed/carboplatin, or pemetrexed alone plus gefitinib. Literature was sourced from electronic databases. Data regarding objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs), treatment-related adverse event grades 3–5 (TRAE 3–5), specific TRAEs [diarrhea, rash, and elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT)] were extracted. The regimens were then ranked using the surface under the cumulative ranking curve (SUCRA). Results: A total of 19 studies involving 4607 EGFR-mutant NSCLC patients were analyzed. In regards to efficacy, pemetrexed/carboplatin (PC) plus gefitinib was superior in ORR and OS to chemotherapy and first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). All the TKI-based regimens had equivalent DCR and PFS. Patients with the L858R mutation treated with PC plus gefitinib achieved a better outcome than most EGFR TKI-related groups (except osimertinib) in the PFS subgroup. In regards to safety, no statistical significance for TRAEs was observed among the eight treatments. In regards to SUCRA, PC plus gefitinib ranked first in terms of PFS, OS, and TRAE grades 3–5. Conclusions: Pemetrexed/carboplatin plus gefitinib is a promising treatment option for EGFR-mutant NSCLC patients in the first-line setting.