Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Combination Therapy as First-Line Treatment for Patients with Advanced EGFR-Mutated, Non-Small Cell Lung Cancer: A Systematic Review and Bayesian Network Meta-Analysis.

(1) Background: Several randomized controlled trials (RCTs) have been conducted in combination with Efficacy and Safety of Epidermal Growth Factor Receptor(EGFR)-Tyrosine Kinase Inhibitor (TKI) for the first-line treatment of patients with advanced non-small cell lung cancer; however, head-to-head comparisons of combination therapies are still lacking. Therefore, this study aims to compare the efficacy and safety of various combination treatments. (2) Methods: We conducted a systematic review and Bayesian network meta-analysis by searching MEDLINE, EMBASE, and COCHRANE for relevant RCTs. (3) Results: TKI combined with antiangiogenic therapy, chemotherapy, or radiation achieved a significant benefit compared with TKI alone for progression free survival (PFS). A combination with radiation yielded better benefits in PFS than any other treatment. In terms of overall survival (OS), only the combination with pemetrexed and carboplatin (HR = 0.63, 95% credible interval 0.43-0.86)/radiation (0.44, 0.23-0.83) was superior to TKI alone. All of the combination therapies may increase the incidence of ≥Grade 3 AEs, as the pooled RRs are over 1; different toxicity spectrums were revealed for individual treatments. (4) Conclusions: The TKI combination of radiation/pemetrexed and carboplatin could provide the best antitumor effects among the first generation TKI-based treatments. Considering safety, ramucirumab and bevacizumab may be the ideal additions to TKIs (systematic review registration: PROSPERO CRD42022350474).