Two new drugs for advanced HER2-positive breast cancer were tested in separate studies, and scientists say they’ve made progress in the development of new treatment options.
This type of breast cancer tests positive for higher levels of a protein called HER2.
One study, published in the New England Journal of Medicine last week, found that adding the experimental drug tucatinib to a chemotherapy regimen consisting of the drugs trastuzumab and capecitabine could improve survival for adults with advanced HER2-positive metastatic breast cancer.
The other study, also published in the New England Journal of Medicine last week, found that the experimental drug conjugate called trastuzumab deruxtecan was able to substantially reduce tumor activity in patients with HER2-positive metastatic breast cancer.
“Both studies are evaluating new drugs for HER2-positive breast cancer, which represents about 15% to 20% of all breast cancers,” said Dr. Eric Winer, chief of the division of breast oncology at Dana-Farber Cancer Institute in Boston and professor of medicine at Harvard Medical School, who was the senior author of the tucatinib study.
“What’s so exciting is we have developed multiple new drugs for HER2-positive breast cancer — we have new drugs for all subtypes of breast cancer — but the changes are most dramatic in the setting of HER2-positive breast cancer,” Winer said.
“It is the single area in breast cancer where we have made the most dramatic progress and continue to,” he said. “For individuals with advanced breast cancer we can individualize therapy more than in the past; it is no longer one size fits all.”
The tucatinib study included 613 patients who previously underwent chemotherapy for HER2-positive metastatic breast cancer by taking the drugs trastuzumab, pertuzumab and trastuzumab emtansine — but that treatment approach had stopped working for the patients.
For the study, the patients were randomly assigned to either the drug tucatinib or a placebo and received chemotherapy with the drugs trastuzumab and capecitabine.
The researchers found that in the first year of treatment, 33.1% of patients in the tucatinib group did not see their cancer progress compared with 12.3% of patients in the placebo group.
The researchers also found that overall survival two years after starting treatment was 44.9% among patients in the tucatinib group and 26.6% among those in the placebo group.
Side effects of the tucatinib treatment that emerged in the study included the risks of diarrhea and elevated levels of an enzyme in the body called aminotransferase.
“But in general it was pretty well tolerated,” Winer said.
Next year, the biotechnology company Seattle Genetics, which develops tucatinib, plans to submit a new drug application to the US Food and Drug Administration and an application to the European Medicines Agency with the goal of bringing this new medicine to the public, Dr. Roger Dansey, chief medical officer at the company, said in a press release on Wednesday.
“Continued innovation to bring new therapies for the treatment of metastatic HER2-positive breast cancer is urgently needed, and we are encouraged by the impressive clinical activity demonstrated with the addition of tucatinib to trastuzumab and capecitabine,” he said in part.
The trastuzumab deruxtecan study included 184 patients who had already undergone multiple prior treatments for HER2-positive breast cancer. The patients were given the recommended dose of trastuzumab deruxtecan at 5.4 mg per kilogram of body weight.
The researchers found that the patients saw no further progression of their cancer for a median of 16.4 months and that the cancer in 60.9% of the patients shrunk by at least 50% in response to the treatment. However, the treatment came with some side effects, including nausea, myelosuppression — the decline of bone marrow activity — and interstitial lung disease.
Overall, “it is rare that a drug has effects on women heavily pretreated,” said Dr. Otis Brawley, Bloomberg Distinguished Professor of oncology and epidemiology at Johns Hopkins University, who was not involved in the new study.
“I am cautiously optimistic,” he said, but added that more research is needed to determine whether trastuzumab deruxtecan could help patients live longer.
Dr. Ian Krop, a principal investigator of the study and associate chief of the division of breast oncology at Dana-Farber Cancer Institute in Boston, called the research results “striking” in a press release on Wednesday.
“These results are particularly striking as trastuzumab deruxtecan prompted a high level of durable tumor reduction among patients, the majority of whom had exhausted most if not all standard therapies for HER2-metastatic breast cancer,” he said. “We are excited by these results and their potential to help patients with this advanced stage of breast cancer.”