By Ayomide Otitoju
A new treatment has shown remarkable promise in nearly halving the risk of disease progression or death in patients with HER2-positive metastatic breast cancer, a less common form of the disease that has seen little therapeutic advancement in over a decade.
The findings, presented Monday at the American Society for Clinical Oncology (ASCO) Annual Meeting, could soon reshape global treatment protocols and establish a new first-line therapy for the advanced stage of HER2-positive breast cancer, which affects roughly 15–20% of all breast cancer patients.
HER2-positive cancers are driven by an overactive HER2 gene, which produces excessive levels of a protein that accelerates cancer cell growth. Once the disease spreads, patients typically face a life expectancy of about five years.
“Seeing such a striking improvement was really impressive to us — we were taking a standard and almost doubling how long patients could have their cancer controlled for,” said Dr. Sara Tolaney, chief of the breast oncology division at Dana-Farber Cancer Institute and lead investigator of the trial.
The current standard therapy, known as THP, combines chemotherapy with two HER2-targeting antibodies. However, the new regimen pairs trastuzumab deruxtecan (T-DXd) — an antibody-drug conjugate — with pertuzumab, a second antibody believed to boost its effectiveness.
Described by Tolaney as a “smart bomb” strategy, T-DXd delivers chemotherapy directly to cancer cells while sparing healthy tissues.
“You can bind to the cancer cell and dump all that chemo right into the cancer cells,” she said. “Some people call them smart bombs because they’re delivering chemo in a targeted fashion — which is how I think we’re able to really increase efficacy so much.”
In the international randomized trial, nearly 400 patients received the T-DXd-pertuzumab combination, while a similar number were treated with the THP regimen. A third group received T-DXd alone, but results for that arm are still pending.
After 2.5 years of follow-up, the combination therapy reduced the risk of progression or death by 44% compared to standard care. The median progression-free survival for the new treatment reached 40.7 months, significantly higher than the 26.9 months for those on THP.
Notably, 15% of patients in the T-DXd group experienced complete remission, nearly doubling the 8.5% seen in the THP cohort.
Side effects reported included nausea, diarrhea, and low white blood cell counts, with a rare but serious complication being lung scarring.
T-DXd is already approved as a second-line therapy after standard treatments fail. The new findings now suggest it could soon become a frontline option, pending regulatory approvals. The results are expected to be submitted to authorities including the U.S. Food and Drug Administration (FDA).
“This represents a new first-line standard treatment option for HER2-positive metastatic breast cancer,” said Dr. Rebecca Dent, a breast cancer expert at the National Cancer Center Singapore, who was not involved in the study.
Tolaney added that future research will focus on determining how long patients — especially those in full remission — should remain on the treatment to optimize long-term outcomes.
