T-DM1 reduces long-term risk of death in HER2-positive breast cancer patients

T-DM1 reduces long-term risk of death in HER2-positive breast cancer patients

In patients with high-risk HER2-positive breast cancer, post-surgery or adjuvant treatment with trastuzumab emtansine (T-DM1) reduced the long-term risk of death or invasive disease by 46% and improved survival compared to trastuzumab alone. According to final results from the Katherine Phase 3 clinical trial, led by researchers at the University of Pittsburgh and UPMC Hillman Cancer Center.

The results, published today in theNew England Journal of Medicine(Nejm), provide long-term evidence for thisNejmIn 2019, which found that TDM1 reduced the risk of death or invasive disease by 50%.

Katherine is a landmark clinical trial that found T-DM1 had such improved activity compared to trastuzumab that results were earlier than expected when the trial was originally designed. The results changed the standard of care worldwide for patients with HER2-positive breast cancer. We continued to follow patients to understand the full magnitude of the benefit and now show that T-DM1 leads to robust long-term improvements in invasive disease-free survival and improves overall survival. “

Charles E. Geyer Jr., MD, senior author, professor in the division of malignant hematology and medical oncology at Pitt School of Medicine, UPMC Hillman and UPMC Magee-Womens Hospital

T-DM1 is an antibody drug conjugate that combines trastuzumab and a chemotherapy drug called emtansine. When trastuzumab attaches to the HER2 receptor on cancer cells, it acts like a Trojan horse, allowing emtansine to penetrate the cancer cells more effectively and kill them from within.

The Katherine study included 1,486 patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer -Tenz targeted agent trastuzumab and surgical removal of the tumor. These patients are at high risk of cancer recurrence and death.

After surgery, patients were randomly assigned to receive standard adjuvant trastuzumab or T-DM1.

After 7 years of follow-up, invasive disease-free survival was 80.8% with adjuvant T-DM1 and 67.1% with adjuvant trastuzumab alone. Overall survival was 89.1% with T-DM1 and 84.4% with trastuzumab alone.

Although adverse events were higher in the T-DM1 group (26.1%) than in patients receiving trastuzumab (15.7%), the overall safety of the drug was considered acceptable.

According to Geyer, a key finding was the consistent benefit of T-DM1 across subgroups of patients. The analysis showed an approximately 50% reduction in the risk of death and invasive disease, regardless of extent of disease at presentation, hormone receptor status, neoadjuvant treatment regimen, pathologic nodal status at surgery, age, and race.

“When I started my career in oncology, we knew that some breast cancers were more aggressive, but we didn’t know why,” Geyer said. “From the excitement of identificationHER2Gene amplification and resulting protein overexpression as targeted oncogene through drug developmentHER2I have had the privilege of being part of the HER2 story, and it is incredibly gratifying to have been part of the research effort that has led to a new standard of care for patients with this disease. “

And this story is still being written. Now Geyer and his colleagues are studying a promising new antibody drug candidate called trastuzumab deruxtcan, or T-DXD, for specific groups of patients, such as patients with lower expression levels of the HER2 protein, who do not respond as well to T-DM1 as patients with high HER2 expression.

“As oncologists, we are greedy,” Geyer said. “We will never be satisfied until we achieve 100% cancer-free survival outcomes for our breast cancer patients.”

Other authors are listed in theNejmPaper.

The Katherine clinical trial was funded by Hoffmann – La Roche/Genentech.

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