Antibody Drug Boosts Survival for Type of Advanced Breast Cancer
A relatively new drug is boosting survival rates for women with a specific type of advanced breast cancer who haven't responded to other treatments, according to a pair of clinical trials.
The targeted antibody drug — trastuzumab deruxtecan (T-DXd, sold under the brand name Enhertu) — dramatically outperformed an older antibody drug in one trial, quadrupling the number of months women survived without their cancer progressing.
T-DXd also outperformed standard chemotherapy in another clinical trial, more than doubling the number of months of progression-free survival and reducing the risk of death by 34%.
T-DXd is aimed at helping patients who have HER2-positive breast cancers.
HER2 is a protein that promotes growth of breast cancer cells. About 20% of patients have tumors with higher levels of HER2.
Results from both clinical trials were reported Wednesday at the San Antonio Breast Cancer Symposium.
“We have a drug that is very effective and seems to be working, at least in good part, by a targeting mechanism against HER2,” said Dr. Carlos Arteaga, chair of comprehensive oncology for the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, in Dallas.
Arteaga, co-director of the symposium, led a news briefing announcing the results of the two trials.
T-DXd delivers a one-two punch to breast cancer cells by combining an antibody called trastuzumab with a chemotherapy drug called deruxtecan.
The antibody part of T-DXd binds with HER2 receptors on the breast cancer tumor, blocking the ability of the protein to promote cancer growth. This binding also serves to steer cancer-killing deruxtecan directly into tumor cells.
The U.S. Food and Drug Administration approved T-DXd in 2019 as a follow-up therapy for patients whose breast cancer had continued to spread despite prior treatments with other cancer drugs.
Ongoing clinical trials have been aimed at figuring out how effective T-DXd is compared to other drugs, and when it should be implemented in treating advanced HER2-positive breast cancers.
One clinical trial compared T-DXd as a follow-up treatment against trastuzumab emtansine (T-DM1), an earlier antibody drug that combined trastuzumab with a different chemo agent.
The 524 patients in that trial randomly were treated with one of the two drugs, after they had stopped responding to initial therapies.
About one in five patients (21%) wound up cancer-free following treatment with T-DXd, compared with nearly 10% of those receiving T-DM1, the researchers reported.
Further, more than 78% had some clinical response to T-DXd, compared with 35% responding to T-DM1.
Patients treated with T-DXd had nearly 29 months of progression-free survival on average, about four times the 7 months seen in patients receiving T-DM1, which is sold under the brand name Kadcyla.
Patients who received T-DXd also had a 36% lower overall risk of death than patients treated with T-DM1, said clinical trial researcher Dr. Sara Hurvitz, a professor with the University of California, Los Angeles, Geffen School of Medicine and Jonsson Comprehensive Cancer Center.
“These updated results do demonstrate remarkable (overall survival) and (progression-free survival) benefits, solidly placing T-DXd as the standard of care,” Hurvitz said in a news briefing.
The other clinical trial compared T-DXd to standard chemotherapy as a follow-up treatment.
The trial involved more than 600 patients whose breast cancers had continued to grow following T-DM1 treatment. About two-thirds received T-DXd, and the rest received chemo.
Breast cancer patients were 64% less likely to die or have their cancer continue to spread following treatment with T-DXd compared to chemotherapy, the researchers found
Average progression-free survival was nearly 18 months with T-DXd, more than twice the 7 months achieved with chemotherapy.
Overall survival also was significantly longer, 39 months on average for T-DXd patients compared to 26 months with chemo.
About 14% of patients wound up cancer-free following T-DXd treatment in this trial, compared to 5% for chemo.
The trial “confirms the favorable benefit/risk ratio of T-DXd in patients with advanced HER2 positive breast cancer,” said clinical trial researcher Dr. Ian Krop, chief clinical research officer at the Yale Cancer Center in New Haven, Conn.
In both trials, the most concerning side effect of T-DXd was damage to the lung, either through inflammation or scarring of lung tissue.
About 6% suffered lung inflammation and 3% lung scarring in Krop's trial, while about 15% suffered lung inflammation or scarring in Hurvitz's trial.
It's not yet clear why the drug would cause these side effects in the lungs, Hurvitz said, noting that it doesn't seem to be driven by the cancer spreading into the lungs.
“We should, as clinicians, continue to follow CT scans of the lungs closely in our patients being treated with T-DXd, because this is an event that can occur even up to a year or longer of a patient being on therapy,” Hurvitz said.
Findings presented at medical meetings should be considered preliminary until published in a peer-reviewed journal.
The American Cancer Society has more about HER2-positive breast cancer.
SOURCES: Carlos Arteaga, MD, chair, comprehensive oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas; Sara Hurvitz, MD, professor, University of California, Los Angeles, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center; Ian Krop, MD, PhD, chief clinical research officer, Yale Cancer Center, New Haven, Conn.; presentation, San Antonio Breast Cancer Symposium, Dec. 6 to 10, 2022