Introduction: One in three women with HER2-positive breast cancer will develop brain metastases, or intracranial metastatic disease (IMD). Historically, treatment of IMD has been confined to surgery and radiotherapy, with a limited role for chemotherapy. However, recent interest has burgeoned in a role for targeted therapy for treatment of IMD. The lack of high-level evidence, such as meta-analyses, regarding the role of targeted therapy in the management of IMD has prevented its inclusion in guidelines directing treatment. We performed a systematic review and meta-analysis to clarify the role of targeted therapy for IMD in women with HER2-positive breast cancer.
Methods: Following PRISMA guidelines, a search of MEDLINE, CENTRAL, EMBASE, Google Scholar, and grey literature sources was conducted by two independent reviewers. Controlled trials and cohort studies that reported survival, safety, or response outcomes for patients receiving HER2-targeted therapy following IMD diagnosis were included. Meta-analyses using a random-effects model were conducted for OS and PFS.
Results: 111 studies reporting on 8226 patients were included. Primary analysis of only RCTs found that HER2-targeted therapy was associated with improved OS (HR 0.63; 95% CI, 0.46–0.86; n = 392) but not PFS (HR 0.75; 95% CI, 0.30–1.85; n = 392) following IMD diagnosis. Secondary analysis combining RCTs and comparative observational studies found that HER2-targeted therapy was associated with improved OS (HR 0.42; 95% CI, 0.35–0.51; n = 2756) but not PFS (HR 0.58; 95% CI, 0.27–1.21; n = 460) following IMD diagnosis. Full analysis will be conducted for all 111 studies for pre-specified outcomes including intracranial PFS.
Conclusion: These findings support a potential role for HER2-targeted therapy in the management of IMD from HER2-positive breast cancer. Final analysis will synthesize current evidence for outcomes of intracranial response, survival, and safety.