New Hope for Patients with Aggressive Breast Cancer
Treatment options began to change in 2017, when the nationwide Keynote-355 trial opened to patients with locally recurrent, unresectable, or advanced TNBC. The study evaluated how well immunotherapy works when added to standard chemotherapy. Phase 3 of the Keynote-355 trial found that combining immunotherapy with chemotherapy helped patients live longer without their cancer worsening, compared with chemotherapy alone, by targeting the PD-L1 protein that some cancer cells use to hide from the immune system. In 2020, the FDA approved this treatment.
The next important study was Keynote-522, which tested the same approach in patients with early-stage TNBC. Results showed a 34 percent lower risk of death, with clear improvements in event-free survival and rates of pathological complete response. This promising result led to FDA approval in 2021.
Today, another major focus is on antibody drug conjugates (ADCs). These drugs are designed to bind to specific proteins on the surface of cancer cells, then release chemotherapy directly into the cells to kill them. As with the Keynote trials, research began in TNBC patients with metastatic disease.
The ASCENT study compared sacituzumab govitecan, a drug that targets the Trop-2 protein found in many cancer cells, to a physician’s choice of chemotherapy in patients whose cancer had not responded to first-line treatments. The results were impressive for both overall and progression-free survival. For example, median survival was 12.1 months with patients receiving the combined therapy versus 6.7 months with chemotherapy alone. The FDA approved sacituzumab govitecan as a second-line treatment in 2023, and the ongoing Ascent-04 trial is evaluating its use as a first-line therapy.
Additionally, another trial, BEGONIA, is studying the combination of datopotamab deruxtecan, an ADC that also targets Trop-2, and durvalumab, an immunotherapy drug that binds to PD-L1.
“It looks to be incredibly effective in phase 1 and 2 trials,” Dr. Danso said. “Nearly 80 percent of metastatic patients showed a confirmed objective response rate.” Researchers are also considering this treatment for early-stage TNBC patients.
Other Advances in Treatment for Triple-Negative Breast Cancer Thanks to Cancer Trial Participation
Virginia Oncology Associates has been part of, or is currently part of, all of those pioneering studies. This is just a small snapshot into the VOA's robust cancer research program. "Results have brought increased hope to patients with virtually all subtypes of cancer", Dr. Danso noted. “They deserve nothing less but the best.”
Virginia Oncology Associates has participated in numerous other clinical trials that are changing the landscape for patients. Among the findings:
- Olaparib and other oral PARP inhibitors, which affect cancer cells’ ability to repair DNA and therefore replicate, have been particularly useful in TNBC patients with a BRCA1 or BRCA2 mutation. In fact, a recent trial showed that another PARP inhibitor, talazoparib, could even replace chemotherapy for some early-stage TNBC patients, with nearly 60 percent showing a complete pathological response.
- Androgen-receptor antagonists, given orally, have shown early promise in fighting a subtype of TNBC characterized by the expression of the Androgen Receptor.
- Trilaciclib, a small-cell molecular inhibitor delivered intravenously, appears to help protect bone marrow and immune function during chemotherapy for TNBC, as demonstrated in a large, randomized Phase II trial. The FDA has already approved its use in patients with extensive-stage small cell lung cancer and is awaiting results of a confirmatory Phase III trial for triple-negative breast cancer .
- Adding alpelisib, a biomarker-driven treatment approach, to chemotherapy could benefit patients with a PIK3CA mutation, which is seen in about 15 percent of TNBC cells. A Phase III trial of the oral medication is underway.
These are just a few examples of the remarkable progress occurring as our understanding of TNBC continues to improve. It is gratifying to be able to offer additional hope to patients with this complex and too-often lethal disease.
Learn more about clinical trials and read some frequently asked questions answered by the cancer specialists at Virginia Oncology Associates.
Related reading: A New Treatment Approach for Triple-Negative Breast Cancer
The Latest in Breast Cancer Treatment Available at Virginia Oncology Associates
If you have been newly diagnosed with breast cancer, the VOA breast cancer specialists are here to develop a personalized breast cancer treatment plan for you. Virginia Oncology Associates' breast cancer treatment services are delivered in a non-hospital setting at one of our easy-to-access locations. We provide the latest cancer treatments and offer second opinions on breast cancer treatment plans. Find a cancer center near you.
Dr. Danso is the Medical Director and Research Director at Virginia Oncology Associates, a regional practice that partners with the U.S. Oncology Network on clinical trials.
Originally published August 2021. Updated January 2026.
