Summary

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• This summary is based on the review of seven systematic review(s)/meta-analysis(es). ^[1-7]
• Tucatinib combined with trastuzumab and capecitabine (TTC) demonstrated an ORR of 47.3% in patients with HER2+ metastatic breast cancer and brain metastases. Trastuzumab deruxtecan (T-DXd) achieved a pooled ORR of 64% (95% CI: 43-85%) in heavily pretreated patients with asymptomatic brain metastases, outperforming other therapies like lapatinib and capecitabine, which had a higher risk of bias.
• For progression-free survival (PFS) and overall survival (OS), tucatinib plus trastuzumab with capecitabine ranked highest, showing superior outcomes compared to other HER2-directed therapies in unresectable or metastatic HER2+ breast cancer. T-DXd ranked first for PFS (HR 0.17; 95% CrI 0.03-0.82), while T-DM1 ranked first for OS in patients with HER2+ breast cancer brain metastases.
• In early HER2+ breast cancer, trastuzumab-based dual anti-HER2 therapy, especially when combined with pertuzumab, significantly improved event-free survival (EFS) and overall survival (OS), with pronounced benefits seen in lymph node-positive subgroups.
• Trastuzumab-based dual anti-HER2 therapy was associated with a higher risk of cardiotoxicity, particularly when combined with pertuzumab (SUCRA of 92%), whereas lapatinib-containing regimens showed more general toxicity but no significant increase in cardiotoxicity.
• Neratinib-containing regimens were generally well-tolerated but showed no significant safety concerns compared to other HER2-targeted therapies, particularly in the management of CNS disease progression.
• There is no population types or subgroups information available in the reviewed studies.