Dataset Information

Comparative Efficacy of Tyrosine Kinase Inhibitors and Antibody–Drug Conjugates in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A Systematic Review and Network Meta-Analysis

ABSTRACT:

Simple Summary

Comparisons between the efficacy of tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs) in treating HER2-positive breast cancer brain metastasis (BCBM) patients have not previously been conducted. We performed a systematic review and Bayesian-based network meta-analysis to pool the estimates of progression-free survival, overall survival, and incidence of central nervous system (CNS) disease progression. The current study indicated that both T-DXd and T-DM1 presented better efficacy than TKIs regarding survival outcomes. Treatments containing neratinib or T-DM1 tended to rank the best in reducing the recurrent rate of CNS. Our study provides more evidence for the clinical decision making for patients with HER2-positive BCBM. More high-quality studies with standardized entry criteria and comparable CNS-related endpoints are warranted in the future.

Abstract

HER2-positive breast cancer brain metastasis (BCBM) is an important clinical problem. A systematic review and network meta-analysis were conducted to compare the efficacy of tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs), two categories of emerging agents in this field. We implemented a comprehensive literature search of PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and abstracts of oncology conferences. A network meta-analysis following Bayesian approaches was performed. Pooled hazard ratios (HRs) and odds ratios (ORs) with credible intervals (CrIs) were calculated to estimate progression-free survival (PFS), overall survival (OS), and the incidence of central nervous system (CNS) disease progression. Sixteen studies were included. Pairwise comparisons of PFS showed salient divergency between T-DXd and the physician’s choice of treatment (HR 0.17; 95% CrI 0.03–0.82) or afatinib (HR 0.14; 95% CrI 0.02–1.00). T-DXd and T-DM1 ranked first regarding PFS and OS, respectively, followed by TKI-containing regimens. The incidence of CNS disease progression was analyzed separately according to baseline BCBM status, among which neratinib-containing regimens were most likely to rank the best. In conclusion, ADCs including T-DXd and T-DM1 showed better efficacy than TKIs in the survival outcomes for HER2-positive BCBM patients. Treatments based on neratinib or T-DM1 revealed favorable results in reducing the recurrent rate of CNS.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9321046 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundBrain metastases (BMs) are frequent events in patients with HER2-positive metastatic breast cancer (MBC) and are associated with poor prognosis. Small-molecule anti-HER2 tyrosine kinase inhibitors (TKIs) are promising agents for the treatment of BM. In this study, we assess the clinical outcomes of patients with HER2-positive MBC and BM treated with TKI-containing regimens compared with those treated with non-TKI-containing regimens.Materials and methodsPubMed, Embase, Cochrane Library, and conference proceedings (ASCO, SABCS, ESMO, and ESMO Breast) were searched up to June 2021. The primary endpoint was progression-free survival (PFS) in patients with BM. Secondary endpoints included PFS in patients without BM and overall survival (OS). The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models.ResultsThis systematic review and meta-analysis included data from 2437 patients (490 with and 1947 without BM at baseline) enrolled in five trials assessing tucatinib-, lapatinib-, pyrotinib-, or afatinib-based combinations. A nonstatistically significant PFS benefit favoring TKI-containing regimens was observed in both patients with BM [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.41-1.12; P = 0.13] and without BM (HR 0.55, 95% CI 0.24-1.26; P = 0.16). Sensitivity analysis, excluding each study singly, demonstrated a significant PFS benefit favoring TKI-containing regimens in patients with BM after the exclusion of afatinib from the analysis (HR 0.56, 95% CI 0.35-0.90; P = 0.016). No statistically significant differences in OS were observed between the comparison groups.ConclusionsA trend in PFS favoring TKI-containing regimens was observed in patients with BM. Sensitivity analysis including only trials that evaluated regimens containing tucatinib, lapatinib, or pyrotinib demonstrated a significant PFS benefit favoring TKI-containing regimens in patients with BM.

Dataset Information

Comparative Efficacy of Tyrosine Kinase Inhibitors and Antibody–Drug Conjugates in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A Systematic Review and Network Meta-Analysis

Simple Summary

Abstract

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets