Reviewing the Latest Advancements in Treatment of TNBC

Lisa A. Carey, MD, ScM, the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research and deputy director of clinical sciences at the University of North Carolina Lineberger Comprehensive Cancer Center, discusses the recent trends in treatment for triple-negative breast cancer (TNBC).

Carey says TNBC has been the hardest subtype of breast cancer to treat, and progress has been slow. However, recently there have been advances in tumor targeting, which was a challenge due to TNBC’s heterogeneity.

Tumor targeting advances include improvements in the application of chemotherapy, along with antibody-drug conjugates such as sacituzumab govitecan (Trodelvy), which has been approved for TNBC, and trastuzumab deruxtecan (Enhertu), which has shown benefit in patients with HER2-low disease in addition to HER2-positive breast cancer. For those with homologous recombination deficiency (HRD), PARP inhibitors are being investigated as a truly tumor-targeted drug, according to Carey.

Immunotherapy has also made an impact, with chemotherapy plus immune checkpoint inhibitor therapy being used in regardless of PD-L1 status in early disease. It is also a preferred frontline therapy for metastatic TNBC in those with high PD-L1 expression, which Carey notes is 40% of those with metastatic disease. The improvements in chemotherapy and immunotherapy are critical for patients as researchers continue to investigate more targeted therapies.

TRANSCRIPTION:

0:08 | TNBC has been the hardest for us to actually show any kind of movement and progress in the metastatic setting where the [overall] survival, until recently, was only about 1 to 2 years. The biggest advances have been really in segregating tumor targeting, which is actually pretty hard to do, because TNBC is a bit of a shapeshifter, and it's a very heterogeneous entity.

0:34 | But the advantages in tumor targeting have come in being better at giving chemotherapy. While we work on truly targeted drugs, we're getting much better given chemotherapy through these antibody-drug conjugates. Things like sacituzumab govitecan and now trastuzumab deruxtecan have really been game-changers in the way we give cytotoxic therapy. I think TNBC is also enriched for those with HRD, and so PARP inhibition—clearly for not just germline, but it looks like somatic BRCA1/2 mutations and maybe some others that are related—seems to be very helpful. That's our one truly tumor-targeted drug.

1:14 | The flip side of that is the importance of immunotherapy. So in TNBC, which is the most immune-activated of all the breast cancer kinds, immunotherapy is now standard for early disease. It doesn't require selection for PD-L1 or anything like that. In the metastatic setting…about 40% of breast cancers are PD-L1–positive in the metastatic setting, and those benefit from the addition of immune checkpoint inhibition to chemotherapy. And...I think both of those are game-changers, both the improvements in the way we give chemotherapy, and also the addition of immune checkpoint inhibition.