Overall Survival Benefits of First-Line Treatments for Asian Patients with Advanced Epidermal Growth Factor Receptor-Mutated NSCLC Harboring Exon 19 Deletion: A Systematic Review and Network Meta-Analysis

SIMPLE SUMMARY: Survival benefits and clinical responsiveness have been exhibited by various generations of EGFR-tyrosine kinase inhibitors (TKIs) in numerous randomized-controlled trials for EGFR-mutated advanced non-small-cell lung cancer (NSCLC) over the past two decades. However, the efficacy, especially long-term overall survival (OS) for Asians harboring an exon 19 deletion (19del) in their NSCLC, remains uncertain. This systematic review and network meta-analysis evaluate the efficacy of all first-line treatments in Asian patients with advanced EGFR-mutated NSCLC harboring 19del. EGFR-TKIs and combination treatments demonstrated no OS benefits in comparison with standard chemotherapy treatments, although progression-free survival (PFS) benefits were revealed. Erlotinib plus bevacizumab, ramucirumab plus erlotinib, and osimertinib are the optimal regimens to prolong PFS for Asians with 19del. Further studies are warranted to investigate the resistance mechanisms and possible strategies for individuals harboring this common mutation. ABSTRACT: (1) Background: Randomized controlled trials (RCTs) have explored various primary treatments for individuals diagnosed as having later-stage epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. Nevertheless, the extent to which such treatments are efficacious, particularly with regard to overall survival (OS) rates of patients from Asia with exon 19 deletion (19del), has yet to be clarified. (2) Methods: A systematic review and frequentist network meta-analysis were conducted by obtaining pertinent studies from PubMed/MEDLINE Ovid, Embase, Cochrane Library, and trial registries, as well as various other sources. RCTs in which two or multiple treatments in the primary setting for patients from Asia with EGFR 19del were compared were included. This research has been recorded in the Prospective Register of Systematic Reviews (CRD 42022320833). (3) Results: A total of 2715 patients from Asia participated in 18 trials in which 12 different treatments were administered, which included: EGFR tyrosine kinase inhibitors (TKIs) (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed-based chemotherapy, pemetrexed-free chemotherapy, and combination treatments (gefitinib plus apatinib, erlotinib plus ramucirumab, erlotinib plus bevacizumab, and gefitinib plus pemetrexed-based chemotherapy). Such treatments were not significantly beneficial in terms of OS for patients from Asia who had 19del. It was demonstrated that erlotinib plus bevacizumab, ramucirumab plus erlotinib, and osimertinib consistently yielded the greatest benefits regarding progression-free survival benefit (P-scores = 94%, 84%, and 80%, respectively). Combination treatments resulted in increased toxicity, particularly gefitinib plus apatinib and erlotinib plus bevacizumab, causing the highest prevalence of grade ≥ 3 adverse events. Icotinib and osimertinib had the fewest grade ≥ 3 adverse events. Specific treatments were associated with a wide range of toxicity levels. (4) Conclusions: In patients from Asia with 19del, both EGFR-TKIs and treatments in which therapies were combined exhibited no OS benefits in comparison with standard chemotherapy treatments. Additional research is required to study TKIs’ resistance mechanisms and possible combined approaches for individuals harboring this common mutation.