First-line treatment for advanced or metastatic EGFR mutation-positive non-squamous non-small cell lung cancer: a network meta-analysis

Abstract

Background: Several head-to-head meta-analyses have compared the efficacy and safety of different first-line treatments in patients with EGFR mutation-positive (M+) advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC). However, there is a lack of comprehensive evaluation encompassing multiple treatment strategies. Our objective is to conduct a network meta-analysis that includes various treatment modalities, enabling both direct and indirect comparisons for a more thorough assessment.

Methods: We conducted a search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception until May 8, 2024, to identify eligible randomized controlled trials (RCTs). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary outcomes included objective response rate (ORR) and grade 3 or higher adverse events (≥3AEs). Stata 15.0 and R 4.3.2 software were utilized for the network meta-analysis.

Results: A total of 30 RCTs, comprising 8654 participants, were included. The study encompassed the following 19 treatments: Chemotherapy; Afatinib; Afatinib + Cetuximab; Apatinib + Gefitinib; Befotertinib; Cetuximab + Chemotherapy; Erlotinib; Erlotinib + Bevacizumab; Erlotinib + Chemotherapy; Gefitinib; Gefitinib + Chemotherapy; Gefitinib + Olaparib; Icotinib; Icotinib + Chemotherapy; Lazertinib; Naquotinib; Osimertinib; Osimertinib + Bevacizumab; Osimertinib + Chemotherapy. The network meta-analysis results indicated that, in terms of PFS, Osimertinib + Chemotherapy (SUCRAs: 93.4%) and Osimertinib (SUCRAs: 84.61%) were the most effective. Regarding OS, Lazertinib (SUCRAs: 89.72%), Gefitinib (SUCRAs: 72.07%), and Osimertinib + Chemotherapy (SUCRAs: 70.74%) emerged as the top three options. Afatinib (SUCRAs: 92.27%) was associated with the best ORR improvement. For ≥3AEs, Afatinib (SUCRAs: 74.93%) and Osimertinib (SUCRAs: 69.42%) were likely the best choices.

Conclusion: Current evidence suggests that, considering both survival and safety, Osimertinib stands out as the preferred first-line treatment for untreated EGFR M + advanced or metastatic nsq-NSCLC. Notably, the combination of Osimertinib with chemotherapy demonstrated superior survival benefits. However, due to the limitations in the number and quality of included studies, these conclusions await further validation through more high-quality research.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024562981, identifier CRD42024562981.

Keywords: EGFR mutation-positive; first-line treatment; network meta-analysis; non-small cell lung cancer; non-squamous.

Figure 1

The PRISMA flowchart of the literature search and selection.

Figure 2

Summary results on risk of bias (using RoB2) of including RCTs. (A), Percent of studies with categories for risk of bias; (B), Summary for the risk of bias in each study.

Figure 3

Network meta-analysis map concerning the efficacy and safety of first-line treatments in patients with EGFR mutation-positive advanced or metastatic non-squamous non-small cell lung cancer on (A) PFS, (B) OS, (C) ORR, (D) ≥3 AEs. The size of the nodes relates to the number of participants in that intervention type, and the thickness of lines between the interventions relates to the number of studies for that comparison. Che, Chemotherapy.

Figure 4

Result of probability ranking for optimal PFS among different intervention measures. The horizontal axis represents the various intervention measures, and the vertical axis indicates the probability of ranking for each intervention measure. Each bar graph shows the probability of different intervention measures being ranked from first position to last position.

Figure 5

Result of probability ranking for optimal OS among different intervention measures.

Figure 6

Result of probability ranking for optimal ORR among different intervention measures.

Figure 7

Result of probability ranking for optimal ≥ 3 AEs among different intervention measures.