Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have shown promising efficacy in clinical trials for resected EGFR mutant NSCLC. However, it is still unclear which type of adjuvant regimens can provide best survival benefit among multiple therapeutic strategies. Herein, we performed a network meta-analysis to comprehensively compare the efficacy and safety of adjuvant treatments for resected EGFR mutant NSCLC.
Studies comparing two or more adjuvant treatments for resected EGFR mutant NSCLC were included. Study outcomes were DFS and OS with hazard ratio and adverse events with odds ratio. The primary endpoint was DFS. Registration number: PROSPERO (CRD42020184514).
10 eligible trials involved 2707 patients and 6 treatments: 3 EGFR-TKIs (osimertinib, erlotinib, gefitinib), TKI following chemotherapy (CT+TKI), chemotherapy alone and placebo. Osimertinib showed the most favorable DFS, with significant superiority versus erlotinib (HR 0.4, 95% CI 0.24-0.66), gefitinib (0.42, 0.26-0.67), chemotherapy (0.23, 0.15-0.33) and placebo (0.17, 0.12- 0.24), but with no significant improvement versus CT +TKI (0.86, 0.42-1.74). CT +TKI provided the best OS benefit across assessable treatments (versus placebo, HR, 0.6 [0.11, 3.34]). OS data form osimertinib was not yet mature. Osimertinib had the fewest toxicity, whereas CT +TKI or chemotherapy alone caused most toxic effects. In subgroup analysis, EGFR-TKIs monotherapy provided more survival improvement for patients with exon 19 deletion than with L858R mutation (HR, 0.31 [0.13, 0.75] for exon 19 deletion, and 0.48 [0.35, 0.65] for L858R mutation, respectively).
These results showed that adjuvant EGFR-TKIs with or without chemotherapy can improve survival outcomes compared with placebo or adjuvant chemotherapy for resected EGFR-mutated NSCLC. Osimertinib provided the most DFS benefits and safety profile among the 6 treatments. Considering both efficacy and toxic effect, osimertinib is a promising agent in adjuvant setting for EGFR-mutant NSCLC, especially for those with exon 19 deletion.
Yi-Long Wu.
This project supported by the Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine (2017B0303141 20 to Y.L. WU), National Natural Science Foundation of China (81872510, 81673031 to W.Z. ZHONG).
All authors have declared no conflicts of interest.