Abstract
Purpose A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Methods PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; P < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; P = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; P = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; P = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; P = 0.002). Conclusion Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.
Highlights
Lung cancer is the most common malignant tumor worldwide and the leading cause of cancer-related death
A total of six randomized controlled trials (RCTs) [12,13,14,15, 19, 20] involving 1,244 patients with Epidermal growth factor receptor- (EGFR-)mutant advanced Non-small-cell lung cancer (NSCLC) who received first-line A + T combination therapy or EGFR-TKI monotherapy were included in this meta-analysis
The present meta-analysis showed that the combination of antiangiogenic inhibitors and EGFR-TKIs significantly prolonged progression-free survival (PFS) in patients with advanced EGFR-mutant NSCLC compared to EGFR-TKIs alone, regardless of EGFR mutation type, brain metastasis status, or Eastern Cooperative Oncology Group (ECOG) performance status (PS) score
Summary
Lung cancer is the most common malignant tumor worldwide and the leading cause of cancer-related death. Non-small-cell lung cancer (NSCLC) accounts for about 85% of lung cancer cases [1]. Epidermal growth factor receptor- (EGFR-) mutant lung cancer accounts for about 10– 30% of advanced NSCLCs and 40–55% of Asian lung adenocarcinoma cases [2]. Clinical studies have confirmed first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) as the standard for first-line treatment of advanced NSCLC patients with EGFR-sensitive mutations, with the progression-free survival (PFS) ranging from 8 to 13.8 months. Second- and third-generation EGFR-TKIs have been approved as the first-line treatment, with PFS of 11–18.9 months [4,5,6,7,8,9]. Patients who initially respond to EGFR-TKIs will inevitably develop disease progression due to secondary drug resistance.
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