Dataset Information

Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR-TKIs in advanced non-small cell lung cancer: A systematic review and network meta-analysis.

ABSTRACT:

Background

The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non-small cell lung cancer (NSCLC). This network meta-analysis was performed to evaluate the differences between them.

Methods

We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outcomes were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS), disease control rate (DCR) and adverse events (AEs). The data of hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were extracted in the studies. A network meta-analysis (NMA) was used to indirectly compare the efficacy and safety of antiangiogenic agents plus EGFR-TKIs and chemotherapy plus EGFR-TKIs.

Results

Pooled data of included studies were demonstrated that chemotherapy plus EGFR-TKIs had a benefit in ORR compared to antiangiogenic agents plus EGFR-TKIs in patients with EGFR mutated NSCLC (RR = 1.1, 95% CI: 1.0-1.2). However, there were no significant differences in PFS, OS and DCR between in the two group (PFS: HR = 1.0, 95% CI: 0.74-1.6; OS: HR = 0.78, 95% CI: 0.45-1.5; DCR: RR = 1.0, 95% CI: 0.94-1.1). The common treatment-related AEs in the two groups were relatively manageable.

Conclusion

Based on the efficacy and safety, the combination of chemotherapy with EGFR-TKIs is considered the best combination treatment options in advanced NSCLC with EGFR mutation.

SUBMITTER: Dai J

PROVIDER: S-EPMC9968601 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR-TKIs in advanced non-small cell lung cancer: A systematic review and network meta-analysis.

Dai Jiali J Liu Xinyin X Li Jun J Qu Tianyu T Cui Yanan Y Jin Shidai S Zhang Erbao E Guo Renhua R

Thoracic cancer 20230102 6

<h4>Background</h4>The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non-small cell lung cancer (NSCLC). This network meta-analysis was performed to evaluate the differences between them.<h4>Methods</h4>We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outco ...[more]

PMID: 36594109

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Project description:Background: Tyrosine kinase inhibitors (TKIs) are standard treatment options for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Increasing clinical investigations have explored the value of EGFR-TKIs plus antiangiogenic drugs as the first-line treatment for EGFR-mutated NSCLC. Methods: We systematically searched PubMed, Cochrane Library, and EMBASE for randomized controlled trials (RCTs) investigating EGFR-TKIs administered with or without antiangiogenic agents for advanced EGFR-mutated NSCLC. The latest RCT that was presented orally at the 2019 European Society for Medical Oncology Congress was obtained online. The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rates (DCRs), and grade 3 or higher adverse events (AEs). Results: We included seven articles on five trials with 1,226 patients. The interventions for the experimental group were the first-generation EGFR-TKI erlotinib combined with bevacizumab (four studies) or ramucirumab (one study), and erlotinib monotherapy (four studies) or erlotinib plus placebo (one study) for the control group. All studies reached their primary study endpoints (i.e., PFS). Compared to erlotinib monotherapy, erlotinib plus antiangiogenic agents remarkably prolonged PFS [hazard ratio (HR) = 0.59, 95% confidence interval (CI) = 0.51-0.69, P = 0.000]; however, ORR, DCR, and OS were similar between the two groups. The overall grade 3-5 AEs increased in combination group (OR = 5.772, 95% CI = 2.38-13.94, P = 0.000), particularly the incidence of diarrhea (OR = 2.51, 95% CI = 1.21-5.23, P = 0.014), acneiform (OR = 1.815, 95% CI = 1.084-3.037, P = 0.023), hypertension (OR = 6.77, 95% CI = 3.62-12.66, P = 0.000), and proteinuria (OR = 13.48, 95% CI = 4.11-44.22, P = 0.000). Additionally, subgroup analysis demonstrated that Asian patients could significantly benefit from combination therapy (HR = 0.59, 95% CI = 0.50-0.69, P = 0.000). Patients with exon 19 deletions (HR = 0.61, 95% CI = 0.49-0.75, P = 0.000) and 21 Leu858Arg mutations (HR = 0.59, 95% CI = 0.47-0.73, P = 0.000) had almost equivalent PFS benefits when treated with double-blocking therapy. Patients with brain metastases at baseline in the combination group had a trend toward better PFS (HR = 0.55, 95% CI = 0.30-1.01, P = 0.001). Conclusions: Erlotinib plus bevacizumab or ramucirumab in EFGR-mutated NSCLC first-line setting yielded remarkable PFS benefits; however, this was accompanied by higher AEs. Epidermal growth factor receptor-TKI plus antiangiogenic agent therapy may be considered a new option for advanced EGFR-mutated NSCLC patients.

Project description:BackgroundRecent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.MethodsTwo hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.ResultsThere were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).ConclusionsAdjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

Dataset Information

Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR-TKIs in advanced non-small cell lung cancer: A systematic review and network meta-analysis.

Background

Methods

Results

Conclusion

Publications

Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR-TKIs in advanced non-small cell lung cancer: A systematic review and network meta-analysis.

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