As research on triple-negative breast cancer (TNBC) has progressed rapidly over the past decade, Virginia Oncology Associates (VOA) has offered women in Hampton Roads early access to emerging therapies through a variety of clinical trials.
Recent and ongoing trials have studied promising new treatment regimens for patients with both early-stage and metastatic TNBC, an aggressive and invasive disease subtype that makes up about 15 percent of all breast cancers.
“We are always trying to do even better than the latest standard of care,” said Michael A. Danso, MD, a Medical Oncologist, Hematologist and Research Director at VOA, based at the Brock Cancer Center in Norfolk. “We’re committed to participating in research that has the power to improve outcomes in many diverse groups of patients.”
TNBC, which is associated with poorer outcomes than other breast cancer subtypes, has been a particularly active area of study. More common in younger and/or Black women, the disease does not respond to either hormone therapy or anti-HER2 drugs.
Historically, TNBC patients have had to rely on chemotherapy alone. That began to change in 2017 when the nationwide Keynote-355 trial opened to patients with locally recurrent, unresectable or advanced TNBC. The randomized, multi-center study looked at the efficacy of adding the immunotherapy drug pembrolizumab (Keytruda) to standard chemotherapy.
The phase 3 trial found that the combination therapy significantly improved progression-free survival compared to chemotherapy alone by targeting the PD-L1 protein, which helps some cancer cells evade immune system detection. In 2020, the FDA granted accelerated approval for the studied patient group.
The next step was Keynote-522, which evaluated the same approach in patients with early-stage TNBC. Data showed a 34 percent reduced risk of death, with significant improvements in event-free survival and pathological complete response; FDA approval followed in 2021.
Today, one major focus is another novel approach: antibody drug conjugates (ADCs), which are built to attach to a specific protein on the surface of cancer cells and then release a cytotoxic chemotherapy agent inside those cells to kill them.
As in the Keynote trials, research started with TNBC patients with metastatic disease. The ASCENT study evaluated sacituzumab govitecan (Trodelvy), a drug that targets the Trop-2 protein overexpressed in many cancer cells, compared against a physician’s choice of chemotherapy in patients who had not responded to first-line therapies.
Again, results were striking for both overall and progression-free survival. For example, median survival was 12.1 months for patients receiving the combination therapy and 6.7 months for the group that had chemotherapy alone. The FDA approved Trodelvy as a second-line treatment in 2023, and the ongoing Ascent-04 trial is studying its value as a first-line therapy.
Another trial, BEGONIA, is investigating the combination of datopotamab deruxtecan (Dato-DXd) – an ADC that also targets Trop-2 proteins – and durvalumab (Imfinzi), an immunotherapy drug that binds to the PD-L1 protein.
“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 using the therapy in early-stage TNBC patients.
VOA has been, or currently is, part of all of those pioneering studies – just a small snapshot into the practice’s robust research. Results have brought increased hope to patients with virtually all subtypes of cancer, Dr. Danso noted: “They deserve nothing less but the best.”
For more information, visit virginiacancer.com
