Breast Cancer Research Highlights at ASCO 2025 With Jasmin Hundal, MD, MS, MPH

SERENA-6: ctDNA-Guided Therapy Switching

The SERENA-6 trial was a phase 3, double-blind, randomized study evaluating the efficacy and safety of switching endocrine therapy based on circulating tumor DNA (ctDNA) detection of ESR1 mutations. The trial enrolled patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer who had an ESR1 mutation during first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor. Patients were randomized to either continue their aromatase inhibitor or switch to camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), while continuing the CDK4/6 inhibitor.

“The most exciting aspect of SERENA-6 is that it uses ctDNA to guide therapy switching before clinical progression, representing a potential shift in how we manage endocrine resistance,” said Dr. Hundal. The primary end point was progression-free survival (PFS), with secondary endpoints including overall survival, quality of life, and safety.

Results were impressive: switching to camizestrant after ctDNA-detected ESR1 mutation significantly improved PFS—16 months versus 9.2 months for those who continued aromatase inhibitor therapy. “This approach more than halved the risk of disease progression or death and delayed deterioration in quality of life,” Dr. Hundal noted. “It’s a very exciting clinical trial because it shows the power of ctDNA-guided therapy, potentially before we see clinical progression.”

VERITAC-2: New Oral SERD on the Horizon

The VERITAC-2 trial, a phase 3 randomized study, compared vepdegestrant A(RV-471), an oral PROTAC estrogen degrader, to fulvestrant in patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer who had progressed after prior endocrine therapy and CDK4/6 inhibitors. Patients were randomized to receive either vepdegestrant or fulvestrant, with the primary end point being PFS in both the intention-to-treat population and the ESR1 mutation–positive subgroup.

“The results were promising, especially in the ESR1 mutation subgroup, where vepdegestrant significantly improved progression-free survival compared to fulvestrant,” Dr. Hundal explained. “While the overall survival data are still immature, it’s exciting to see a new oral SERD with a different mechanism—PROTAC technology—emerging as a potential option.”

Communicating With Patients: What to Share Now

With these advances still in development, Dr. Hundal reflected on how to approach patient conversations. “We get a lot of questions in clinic about ctDNA and how it’s being used,” she shared. “While we’re not yet using it in asymptomatic patients, as in SERENA-6, it’s important to be aware of these advances because they’re likely to become more relevant in the near future. I’m very hopeful that as more studies are conducted and more results become available, ctDNA will be more readily used in the clinic and accessible for our patients.”

Regarding new therapies like vepdegestrant, Dr. Hundal added, “It’s really an innovative oral medication that uses a different technology to degrade the estrogen receptor. It’s interesting to see more options emerging beyond fulvestrant and other drugs we’ve used for years.”

Key Takeaways

• ctDNA-guided therapy switching (SERENA-6) may soon allow clinicians to intervene before clinical progression, improving outcomes for patients with ESR1 mutations.
• New oral SERDs like vepdegestrant (VERITAC-2) are showing promise, particularly for patients with ESR1 mutations who have progressed on prior therapies.
• Staying current with emerging data is crucial, as these advances are likely to impact clinical practice in the near future.

As Dr. Hundal concluded, “There were a lot of exciting advancements presented at ASCO, and I look forward to more updates at future conferences. These studies are paving the way for more personalized and effective breast cancer care.”

About Dr. Hundal

Jasmin Hundal, MD, MS, MPH, is a second-year Hematology/Oncology Fellow at the Cleveland Clinic in Cleveland, Ohio. Previously, she completed her Internal Medicine Residency at the University of Connecticut. Dr. Hundal’s main area of interest is the overlap between cardiometabolic health and cancer, particularly for breast cancer patients and survivors. Outside of work, she enjoys traveling, cooking, and hiking.