The trial randomized 557 patients with low expression of HER2 and who had previously received one or two lines of chemotherapy. Nearly 89% had HR-positive disease, while the remaining 11% were HR-negative. Patients were given either Enhertu or “physician’s choice” of one of five different chemotherapies.

The study’s main goal was to show Enhertu could slow cancer progression compared to chemotherapy in HR-positive patients. Secondary measures assessed survival in HR-positive patients as well as in all participants, and disease progression in the overall group. Enhertu met each goal, with an effect size that Dana-Farber’s Lin described as “quite dramatic.”

After a year and a half of follow-up, researchers found Enhertu had held tumors in check for a median of 10.1 months among those whose cancers were HR-positive, roughly twice as long as another round of chemotherapy.

These HR-positive patients lived a median of just under two years versus about 18 months for those given chemo.

HR-negative patients also benefited from treatment, going a median of 8.5 months without their tumors growing compared to 2.9 months for the chemotherapy group. They lived about 10 months longer than those on chemo, with overall survival in the former group reaching a median of 18.2 months compared to 8.3 months in the latter. Similar-sized benefits were reported in the overall study population as well.

However, the drug can be difficult to take. Before prescribing Enhertu, Lin tells patients it “feels like chemotherapy,” with similar side effects like hair loss, nausea and blood count issues. Though severe side effects were more common with chemotherapy than Enhertu, drug-related lung scarring known as interstitial lung disease, or pneumonitis occurred in about 12% of Enhertu-treated patients and was fatal for three of them. One patient on chemo had lung side effects.

The drug’s safety profile means physicians should be careful prescribing to those with severe underlying lung disease, Moore said. “We need to be cautious, for sure,” Jacot added.

But he, Lin and Moore felt Enhertu’s clear benefits make treatment worthwhile and expect the drug will be widely used. Doctors are getting better at quickly identifying and managing the lung side effect, too, Lin said.

Now they’ll need to figure out who is “HER2 low,” something ASCO breast cancer expert Jane Lowe Meisel called in a statement a “new category in breast cancer” because of the study results.

“We need to create a new classification,” said Jacot. “We clearly need to make everybody think that HER2 low is something different.”