Emerging Therapies in Metastatic Breast Cancer

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Novel and emerging therapies are currently being investigated to treat patients with metastatic and triple-negative breast cancer. These trials are examining new approaches to antiangiogenic therapy, PARP inhibitors, and the introduction of immunoconjugates.

Several antiangiogenic therapies are currently being investigated for patients with breast cancer, including bevacizumab, sorafenib, and tivozanib.

Joyce A. O’Shaughnessy, MD, describes several trials, including the phase III MERiDiAN trial that is investigating bevacizumab in patients stratified by plasma VEGF-A levels. This trial hopes to discover a predictive biomarker for the use of bevacizumab. In general, patients with triple-negative breast cancer (TNBC) seem to have higher levels of plasma VEGF-A, suggesting a higher response to bevacizumab.

Several trials are examining combination strategies with sorafenib, an antiangiogenic therapy that inhibits VEGFR, PDGFR, and Raf kinases. William J. Gradishar, MD, believes the most promising is the phase III RESILIENCE trial that is comparing capecitabine plus sorafenib to capecitabine and placebo for patients with advanced breast cancer.

In addition to antiangiogenic therapies, several PARP inhibitors and immunoconjugates are also under investigation. Patients with BRCA mutations seem to be particularly sensitive to PARP inhibitors, even when given as a monotherapy, Gradishar points out. O'Shaughnessy adds that PARP inhibitors may even be effective more generically in patients with double-strand DNA repair problems and not exclusively BRCA mutations.

In TNBC, the main concern remains finding druggable targets. Linda T. Vahdat, MD, believes the immunoconjugate glembatumumab vedotin (CDX-001) shows potential in TNBC by targeting GPNMB.