New drug shows strong activity against brain metastases in HER2-positive breast cancer

A drug that delivers chemotherapy on to tumors has proven spectacular exercise towards a number of the hardest-to-reach most cancers cells: those who have unfold to the mind in sufferers with superior HER2-positive breast most cancers. The findings, from a world scientific trial led by Dana-Farber Most cancers Institute researchers, reinforce earlier findings of the advantages of the drug – trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate – in these sufferers, trial leaders say.

The outcomes of the trial, dubbed the DESTINY-Breast12 examine, have been introduced in the present day on the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain, and printed concurrently in a paper within the journal Nature Medication.

The findings level to T-DXd as a priceless new remedy choice for sufferers with a very difficult type of most cancers, researchers say. “As many as half of sufferers with HER2-positive breast most cancers develop mind metastases, which regularly has a poorer prognosis than breast most cancers that hasn’t unfold to the mind,” says Nancy Lin, MD, chief of the trial and senior writer of the examine in Nature Medication. Lin is the affiliate chief of the Division of Breast Oncology, Dana-Farber, Susan F. Smith Heart for Ladies’s Cancers, and the director of the Metastatic Breast Most cancers Program. Localized therapies resembling surgical procedure, radiosurgery, and radiation remedy to the mind, are used to deal with mind metastases, however the illness normally progresses within the central nervous system – the mind and spinal wire – inside six to 12 months of remedy.

Trastuzumab deruxtecan consists of the drug deruxtecan – a chemotherapy agent – linked to an antibody that targets the HER2 protein on breast most cancers cells. Trastuzumab itself is a mainstay remedy of HER2-positive breast most cancers that has unfold to different elements of the physique, together with the mind. However as with therapies directed particularly on the mind, sufferers receiving trastuzumab normally have their illness progress, typically within the central nervous system.

Extra systemic therapies for sufferers with mind metastases are urgently wanted.”

Nancy Lin, MD, chief of the trial and senior writer of the examine

The DESTINY-Breast12 trial concerned 504 sufferers with HER-2 optimistic breast most cancers handled at 78 most cancers facilities in Western Europe, Japan, Australia, and the U.S. 200 sixty-three individuals had energetic or steady mind metastases and 241 had no mind metastases. All had obtained not less than one remedy earlier than enrolling within the trial.

After a median follow-up of 15.4 months, progression-free survival of individuals with mind metastases – the size of time sufferers lived with the most cancers earlier than it worsened – was a median of 17.3 months, investigators discovered. 12- month progression-free survival was 61.6%. Seventy-one % of individuals had an intracranial goal response – a measurable lower of their most cancers within the central nervous system. As anticipated, there was additionally a excessive charge of response in tumors exterior of the central nervous system in sufferers with or with out mind metastases. Ninety % of sufferers in each teams have been alive a 12 months after starting T-DXd remedy.

The unintended effects related to T-DXd have been according to these reported in earlier research and included nausea, constipation, neutropenia (low ranges of a kind of white blood cells), fatigue, and anemia. Interstitial lung illness (ILD), a recognized danger of T-DXd, was noticed at comparable charges to prior research, and vigilance to this doubtlessly deadly aspect impact stays essential.

“Our information present that T-DXd has substantial and sturdy exercise inside the mind in sufferers with HER2-positive breast most cancers that has metastasized there,” Lin says. “These outcomes assist using the drug going ahead on this affected person inhabitants.”