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‘Dramatic’ study results for AstraZeneca, Daiichi drug suggest new way to treat breast cancer

Twenty-four years ago, a drug called Herceptin changed how doctors treat breast cancer. Its approval in 1998 made it possible to target the aggressive breast tumors tied to a gene called HER2.

Other drugs quickly followed Herceptin and, over the years since, have substantially improved survival for people with the disease.

A quarter of a century later, another shift in treatment could be on the horizon. At the American Society of Clinical Oncology meeting, AstraZeneca and Daiichi Sankyo are presenting results proving that, for the first time, a targeted medicine can help metastatic breast cancer patients whose tumors express only low levels of HER2.

Clinical trial data revealed at ASCO and published in The New England Journal of Medicine Sunday show the drug, Enhertu, halved the risk of cancer progression compared to chemotherapy and reduced the risk of death by 36%.

“This is really, really impressive,” said William Jacot, a study investigator and medical oncologist at the Montpellier Cancer Institute. “I was not expecting something near so good to be achievable with HER2 breast cancer.”

Halle Moore, another investigator and the director of breast medical oncology at the Cleveland Clinic’s Taussig Cancer Institute, said some patients achieved an even greater benefit. The survival numbers, she added, are “extremely meaningful.”

There are important caveats, however. Enhertu is associated with a type of lung scarring that can require stringent monitoring to detect and manage. In a few cases in the trial, this side effect led to death. The length of follow-up is also relatively short, so it’s unclear just how long benefits might endure. It’s unknown exactly what level of HER2 expression is required for Enhertu to work, or how helpful the drug might be for so-called triple-negative patients, who have particularly fast-moving disease.

Nonetheless, the results are expected to change breast cancer treatment, according to experts interviewed by BioPharma Dive. HER2 expression has long been considered in binary terms, with a patient diagnosed as either “positive” or “negative.” Yet about half of metastatic breast cancer patients are somewhere in between, with tumors that have low, but still detectable levels of the protein. These patients don’t benefit from drugs like Herceptin and chemotherapy is the typical treatment for many.

Enhertu could become the first HER2-targeting medicine available to these patients. It could also shift how breast cancer is categorized, making it important to know not only whether tumors are HER2-positive, but exactly how much protein they express.

“It’s going to really significantly change our standard of care,” said Nancy Lin, a medical oncologist specializing in breast cancer at the Dana-Farber Cancer Institute. “In general, everyone who has metastatic disease is going to need to know their HER2 status,” and whether it’s defined as “positive, low, or zero.”

Lin wasn’t involved with the trial but is an investigator in a different Enhertu study and has consulted for AstraZeneca.

AstraZeneca and Daiichi, which first claimed study success in February but held off presenting details, have said they intend to submit the results to regulators as soon as possible. In low expressers, the Food and Drug Administration has already granted the drug a Breakthrough Therapy designation, a regulatory tool that is used to speed up reviews.

Improving prospects

The HER2 gene was first discovered and linked to breast cancer in the 1980s, when the protein it expressed was found in high levels on certain tumors. That finding led, in halting steps at academic centers and at the biotech company Genentech, to the drug that would become Herceptin.

Results from early breast cancer trials of Herceptin were so striking they sparked patient protests demanding faster access. Follow-up study confirmed a powerful benefit and the FDA approved Herceptin soon after, establishing “HER2-positive” as a treatable breast cancer type. Drugmakers, including Genentech’s eventual owner Roche, developed successor medicines like Perjeta and Kadcyla.

Published June 5, 2022

Ben Fidler, Senior Editor

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