Trastuzumab deruxtecan improves PFS in metastatic breast cancer, but ups ILD risk

Treatment with trastuzumab deruxtecan (T-DXd) demonstrates efficacy in patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) breast cancer but may result in adverse events, such as interstitial lung disease (ILD), suggests a study.

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. 

The authors did a comprehensive search across PubMed, Scopus, and Web of Science through January 2024 for clinical trials assessing the efficacy and safety of T-DXd. The eligibility criteria were based on the PICOS framework. Studies that met these criteria were assessed for quality and extracted for data.

Progression-free survival (PFS), overall survival (OS), and incidence of adverse events were the primary outcomes. A random-effects meta-analysis was conducted to synthesize data.

Seven studies, with a total of 2,201 patients, were included in the pooled analysis, which found that T-DXd use resulted in significantly better PFS (odds ratio [OR], 0.37, 95 percent confidence interval [CI], 0.27–0.52), indicating its efficacy in slowing disease progression.

Although efficacious, T-DXd use also led to an increased risk of anaemia (OR, 2.10, 95 percent CI, 1.36–3.25), fatigue (OR, 1.56, 95 percent CI, 1.21–2.02), nausea (OR, 6.42, 95 percent CI, 4.37–9.42), vomiting (OR, 6.21, 95 percent CI, 3.14–12.25), constipation (OR, 2.26, 95 percent CI, 1.53–3.34), and ILD (OR, 10.89, 95 percent CI, 3.81–31.12).

Of note, the efficacy outcomes showed significant heterogeneity, which was addressed through sensitivity analysis.

“These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks,” the authors said. “Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.”