Comparison of the efficacy and safety of first-line treatments for of advanced EGFR mutation-positive non-small-cell lung cancer in Asian populations: a systematic review and network meta-analysis

Abstract

Background: According to the 2023 guidelines for treating non-small-cell lung cancer (NSCLC), first-line treatment and recently developed agents for the treatment of epidermal growth factor (EGFR) mutation-positive locally advanced or metastatic NSCLC were compared in this meta-analysis. Treatment regimens involved in the included studies included first, second, and third-generation tyrosine kinase inhibitors (TKIs), TKIs plus chemotherapy, TKIs plus angiogenesis inhibitors, and platinum-containing doublet chemotherapy with or without bevacizumab. Considering the varying efficacy and safety of drugs in people of different ethnic origins, the optimal regimen should be determined, and the safety of first-line treatments should be assessed in the Asian population specifically.Methods: PubMed, Embase, the Cochrane Library, Web of Science, and the China National Knowledge Infrastructure (CNKI) were systematically searched to retrieve reports on randomized controlled trials (RCTs) with research data published from inception to 1 February 2023. Adopting Asian patient populations as the target (including studies in which Asian patients accounted for more than 50% of the sample), a network meta-analysis (NMA) was conducted for comparison of treatment regimens and treatments were ranked based on the surface under the cumulative ranking curve (SUCRA).Results: A total of 19 RCTs involving 5,824 patients and covering 14 treatment regimens were included. The primary outcome measure examined in this study was progression-free survival (PFS); other outcome measures examined were overall survival (OS), disease control rate (DCR), objective response rate (ORR), occurrence of any adverse events (AE), occurrence of adverse events of grade 3 or above (≥3AE), and occurrence of serious adverse events (SAE). In terms of PFS, all regimens including TKIs (as a monotherapy or in combination with other therapies), as well as bevacizumab (Bev) plus chemotherapy (Ch) were found to be significantly superior to basic chemotherapy (HRs: 0.09–0.61, p < 0.05 in all cases compared with Ch alone). The highest-ranking therapies were erlotinib (Erl) plus Bev (SUCRA: 0.94) and Erl plus ramucirumab (Ram) (SUCRA: 0.93). Regarding OS, no significant differences was observed between first-line treatment strategies; the top four treatments based on SUCRA, in rank order, were Bev + Ch (0.87), gefitinib (Gef) plus Ch (0.81), dacomitinib (Dac) (0.79), and osimertinib (Osi) (0.69). Additionally, there were no significant differences between first-line treatment strategies in terms of DCR. Regarding ORR, the top three treatments based on SUCRA were Erl + Bev (0.85), Erl + Ram (0.76), and Gef + Ch (0.74). No significant difference between first-line treatment strategies was observed in terms of the risk of AE. However, based on SUCRA, Erl ranked highest on avoidance of ≥ 3AE (0.97), and Osi ranked highest on avoidance of SAE (0.91).Conclusion: Based on these analyses of survival benefits, tumor burden response, and safety, furmonertinib (Fur), Osi, and aumolertinib (Aum) may represent the best treatment regimen options for Asian patients, significantly prolonging survival (as measured by median PFS/OS), eliciting a greater tumor burden response, and exposing patients to a lower risk of adverse events. Although Erl + Bev and Erl + Ram are associated with the best survival benefits in terms of PFS, further clinical studies are still needed to identify ways to reduce the risk of adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42023407994, identifier CRD42023407994

Effectiveness and safety of the bevacizumab and erlotinib combination versus erlotinib alone in EGFR mutant metastatic non-small-cell lung cancer: systematic review and meta-analysis

“…Our results report a similar HR in PFS, but slightly lower in OS, and our results (evaluated in the first-line setting) found a benefit of the combination in ORR (RR: 0.79; p = 0.003). A network meta-analysis ( 53 ) aimed at comparing different first-line regimens for NSCLC treatment in an Asian population found that the highest scoring regimens were erlotinib (Erl) plus Bev (SUCRA: 0.94) and Erl plus ramucirumab (Ram) (SUCRA: 0.93) (but only one study) compared to bevacizumab alone (SUCRA: 0.87). These results, which are like those found in our study, suggest that while there are benefits in terms of PFS, the combination may carry additional risks that should be considered but can be considered as a good therapeutic option.…”

Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations

“…NSCLC patients treated with ex20ins had an overall ORR of 53.5%, a DCR of 100%, and a 3-month PFS rate of 100% in 15 patients treated with furmonertinib. A phase III, randomized, multicenter, open-label study, FURMO-004 (NCT05607550), evaluating furmonertinib versus platinum-containing chemotherapy in the first-line treatment of EGFR ex20ins mutations NSCLC is ongoing ( 51 ). We anticipate that additional large-scale clinical studies will achieve improved efficacy.…”

Furmonertinib for EGFR-mutant advanced non-small cell lung cancer: a glittering diamond in the rough of EGFR-TKI

“…The EGFR exon 19 deletion (19 del) and exon 21 L858R mutation (21 L858R) account for approximately 90% of EGFR mutations, which are commonly referred to as classical EGFR mutations. A network meta-analysis found that furmonertinib, osimertinib, and aumolertinib may represent the optimal treatment for Asian patients, due to prolonged survival, greater tumor burden response, and lower risk of adverse events ( Chen et al, 2023 ). For advanced NSCLC with classical EGFR-mutations, the first-line treatment of osimertinib, aumolertinib, and furmonertinib achieved median progression-free survival (mPFS) of 18.9, 19.3, and 20.8 months, respectively, in comparison with gefitinib or erlotinib ( Soria et al, 2018 ; Shi et al, 2022a ; Lu et al, 2022 ) ( Table 1 ).…”