When breast cancer is classified as HER2 positive, it means that this cancer kinesin is abundant on the cell surface.This protein discovery Cause cancers are defined in a binary way – they either have HER2 or they don’t. Research has led to many drugs that block this protein, but the problem is that in about half of breast cancers, its levels are too low for HER2-targeting drugs to help.
Partners AstraZeneca and Daiichi Sankyo now have clinical data showing their HER2-targeting drug Enhertu can treat so-called “HER2-low” breast cancer. result A pivotal study showed that their drug cut the risk of disease worsening or death by nearly half. The data were presented Sunday at the annual meeting of the American Society of Clinical Oncology in Chicago. post Also published in the New England Journal of Medicine.
“We haven’t had targeted therapy in this group of patients, which is a large subgroup of patients,” Shanu Modi, a medical oncologist at Memorial Sloan Kettering Cancer Center and the study’s principal investigator, said at a media briefing. . result. “We’ve always treated them as HER2 negative. I think that’s why these data are so important. This is the first time we’ve been able to expand HER2-targeted therapy to an entirely new population of breast cancer patients.”
Enhertu’s phase 3 trial enrolled 557 patients with HER2-low, metastatic breast cancer who had been treated with one or two earlier chemotherapy regimens. Patients were randomly assigned to receive the study drug or chemotherapy of the physician’s choice. The primary goal is to assess progression-free survival, which is how long a patient can live without the disease getting worse. Median progression-free survival was 10.1 months in the Enhertu group and 5.4 months in the group receiving chemotherapy. This reduced the risk of disease progression or death for the investigational drug by 49%.
Enhertu belongs to a class of drugs called antibody drug conjugates (ADCs), which consist of targeted antibodies linked to a payload of anticancer drugs. The drug pairs the antibody trastuzumab with deruxtecan, a drug that causes cells to die by damaging their DNA. This ADC was originally developed by Daiichi Sankyo.AstraZeneca start cooperation The drug was studied in 2019. Later that year, the FDA awarded Enhertu expedited approval As a treatment for HER2-positive breast cancer that has not responded to at least two early-stage HER2-targeted therapies.
The partners share in the development and commercialization of Enhertu globally, with the exception of Japan, where Daiichi Sankyo owns all rights.A month ago, the FDA approved the drug as a second-line treatment for HER2-positive breast cancer, a decision that also translates into accelerated approval. fully approved.
Jane Meisel, a professor of hematology and oncology at Emory University School of Medicine and an ASCO breast cancer specialist, said she has seen Enhertu used as a second-line treatment for patients with HER2-positive cancers with good results. She added that the new data on HER2-low breast cancer means the drug’s benefits extend to a new group of patients whose cancers are very difficult to treat or have progressed after multiple lines of therapy. “I think the results of this trial will obviously change practice,” Messer said in the briefing.
Modi described Enhertu as a next-generation ADC, saying it “has advanced pharmaceutical properties compared to our other HER2 therapies, not just antibody drug conjugates.” She specifically pointed to Enhertu’s ability to carry a high drug payload . The drug’s linker technology also brings advantages to the drug. She explained that Enhertu’s linker releases the payload in such a way that the drug retains its ability to penetrate HER2-positive cells and other cells that may not even express HER2.
Enhertu does have some risks. Clinical tests have shown that some cases of interstitial lung disease can cause scarring and inflammation. For most patients, this lung toxicity was low-grade and reversible, Modi said. No high-grade events were reported in the pivotal trials that led to the drug’s approval as a second-line treatment. In the latest results reported this weekend, Modi admitted three deaths. But she said the incidence of serious toxicities is falling and is now lower than the clinical trials that supported Enhertu’s original approval. Modi added that the way clinicians deliver this treatment is to select patients best suited for treatment, monitor pulmonary toxicity and manage it as it develops.
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