The outlook for people with HER2-positive (HER2+) metastatic breast cancer (MBC) has improved significantly over the past decades thanks to recent advancements in research, including the development of HER2-targeted therapies. While these treatments do extend the life of many patients, they can also bring adverse side effects, high costs and the inconvenience of regular visits to the clinic.
Recent studies have shown that some people with HER2+ MBC do not experience growth or spread of their cancer 8 to 10 years after treatment (meaning their cancer hasn’t gotten worse). Known as “exceptional responders,” these patients respond well to standard therapy. However, doctors cannot predict which of these patients can stop their treatment safely.
“We have patients who are surviving for decades on treatment for HER2-positive metastatic breast cancer, but no one has studied whether it’s safe, and in whom it might be safe to stop their anti-HER2 therapy,” says Komen-funded researcher Heather Parsons, M.D., M.P.H., a medical oncologist at Dana-Farber Cancer Institute.
Dr. Parsons is the principal investigator for the STOP-HER2 clinical trial, a study that is exploring whether stopping anti-HER2 treatments at the right time could lead to better outcomes for patients, including reduced toxicities and improved quality of life.
The STOP-HER2 Clinical Trial
Sponsored in part by Komen, the STOP-HER2 clinical trial is a single arm, phase 2 study that is investigating whether it is safe for some people with HER2+ MBC to stop their anti-HER2 therapy. Study participants must be exceptional responders to their first line of treatment and have been progression-free for the last 3 years of their standard therapy, with a few exceptions.
The STOP-HER2 trial has two different groups of participants. The first group of 30 patients will continue their standard treatment, while the second group of 52 patients will stop their treatment completely and will be watched closely to see if their cancer comes back. Both groups will have regular checkups and blood screenings every three months, as well as questionnaires and body scans.
Throughout the study, Dr. Parsons and her team will analyze participants’ blood samples for specific biomarkers that provide a real-time snapshot of tumor activity. After one year, Dr. Parsons will evaluate the biomarkers in both groups for evidence of progression-free survival, or no additional spread of cancer cells. Using this unique data, she hopes to identify who should continue their anti-HER2 treatment and who can safely stop.
“If STOP-HER2 is a very positive or very successful study, I think it is something that could potentially change therapy for patients with HER2-positive metastatic breast cancer who match the study population, and I’m hopeful for that,” Dr. Parsons says.
Personalizing Treatment with ctDNA
In the STOP-HER2 trial, Dr. Parsons is focusing on the use of blood-based biomarkers called circulating tumor DNA, or ctDNA, as a tool to identify which patients can successfully stop their treatment without a change or progression of their cancer.
“The hypothesis is that if a cancer is present and active, it would be releasing ctDNA into the blood,” Dr. Parsons says. “Even very low levels would be detectable, and if it’s detectable, it might show that someone’s disease is active, and they should not stop treatment.”
As tumors grow, some cells die and break down, releasing small fragments of ctDNA into the bloodstream. By measuring the amount of ctDNA in the blood, researchers can identify signs of possible recurrence or disease progression even earlier than standard imaging.
“We don’t know if ctDNA will correlate with outcomes, but based on a lot of data that we have from other studies, we think it’s a reasonable thing to consider,” Dr. Parsons says. “We’re hopeful that we’ll be able to use it going forward.”
Better Outcomes and Quality of Life
Stopping standard anti-HER2 therapy could mean better outcomes for patients, including reduced side effects, less financial toxicity and less time spent on visits to the clinic for treatment. While anti-HER2 treatments are not the most toxic therapies, patients are committed to going to their doctor every three weeks to get IV treatments.
Targeted therapies for HER2+ breast cancer, such as trastuzumab and others, can also be very expensive. While anti-HER2 drugs are generally covered by insurance in the U.S., not all patients have adequate insurance coverage, and out-of-pocket costs can be extremely high.
“These drugs still cost thousands of dollars, and that can really add up, especially for a drug that someone’s on indefinitely,” Dr. Parsons says.
For participants of the STOP-HER2 trial, there is much promise on the horizon for better outcomes and improved quality of life. And with less time spent in treatment, there is more time for patients to focus on the things in their lives that really matter.
“HER2-positive breast cancer really had the worst outcomes or was among the worst outcomes for patients,” Dr. Parsons says. “Now, to see that patients are asking the question, ‘Can somebody just stop their treatment?’ is incredible. That’s a sign of what is what is possible for patients, and what is to come.”
Trial fact sheet HERE.
