Tissue-agnostic drug approvals: how does this apply to patients with breast cancer?

Area of Science:

• Oncology
• Genomics
• Precision Medicine

Background:

• Tissue-agnostic therapies represent a paradigm shift in oncology, targeting specific genomic alterations regardless of tumor origin.
• The FDA has approved agents like pembrolizumab, larotrectinib, and entrectinib for tumor-agnostic indications based on biomarkers such as microsatellite instability, high tumor mutational burden, and NTRK fusions.
• Genomic alterations targeted by these therapies are infrequently found in breast cancer, with limited data on their effectiveness in advanced disease.

Purpose of the Study:

• To review the prevalence of key genomic targets for tissue-agnostic therapies in breast cancer.
• To discuss methods for detecting these specific genomic alterations.
• To evaluate the clinical characteristics of breast cancer patients with these alterations and summarize available efficacy data for targeted agents.

Main Methods:

• Literature review focusing on studies investigating tissue-agnostic therapy targets in breast cancer.
• Analysis of prevalence data for microsatellite instability, high tumor mutational burden, and NTRK fusions in breast cancer.
• Examination of clinical trial data and case reports on the efficacy of pembrolizumab, larotrectinib, and entrectinib in breast cancer patients with relevant genomic alterations.

Main Results:

• The prevalence of microsatellite instability, high tumor mutational burden, and NTRK fusions is generally low in breast cancer.
• Detection methods include next-generation sequencing, immunohistochemistry, and PCR-based assays.
• Limited but emerging data suggest potential efficacy for these agents in select breast cancer populations, though further research is warranted.

Conclusions:

• Tissue-agnostic therapies offer a potential treatment avenue for a subset of advanced breast cancer patients with specific genomic alterations.
• Understanding the prevalence and detection of these biomarkers is crucial for clinical application.
• Further clinical investigation is needed to establish the role and optimize the use of these targeted agents in breast cancer management.