New Therapies for Women With HER2-Positive Breast Cancer

An investigational drug appears to be effective for women with breast tumors that express the HER2 protein (also known as HER2-positive breast cancer) and who have had the disease progress after receiving other treatments, including other HER2-targeted drugs. The phase 2 study results were presented December 11, 2019, at the San Antonio Breast Cancer Symposium (SABCS).

HER2-positive breast cancer is a common form of the disease, affecting about 1 in 5 women who are diagnosed with breast cancer. Women with the disease have tumors that produce higher levels of the HER2 protein, which sits on the outside of breast cells.

Detected early, HER2-positive cancers are amenable to a number of drug treatments, but these cancers tend to progress faster than other breast cancers, and metastatic disease poses treatment challenges because patients often develop resistance to medication.

The new study, published simultaneously in The New England Journal of Medicine, provides a potentially life-extending option for HER2-positive patients in whom cancer has developed resistance to the standard medication, said Ian Krop, MD, PhD, lead author of the study and associate chief of the division of breast oncology at Dana-Farber Cancer Institute in Boston.

The study included 253 patients with metastatic HER2-positive breast cancer who were previously treated with the drug Kadcyla (T-DM1 or trastuzumab emtansine) and other HER2-targeted medication, such as trastuzumab (Herceptin, Herzuma, or Igivri) and Perjeta (pertuzumab). The patients, on average, had received six prior treatments for advanced cancer. Among the study group, 184 patients received the investigational medication, called trastuzumab deruxtecan, or T-Dxd.

Trastuzumab deruxtecan is similar to Kadcyla in that it features a monoclonal antibody, essentially a lab-made antibody, designed to target the HER2 protein on cancer cells. Trastuzumab deruxtecan delivers an agent known as a topoisomerase 1 inhibitor to attack cancer cells. The payload drug is about 10 times more potent than similar drugs in its class and has typically not been used to treat breast cancer, Dr. Krop said.

The study showed a 60.9 percent response rate in patients receiving trastuzumab deruxtecan. Six percent of the patients had a complete response to the treatment, meaning that there was no evidence of disease. Just under 55 percent of the patients had partial responses to the treatment, meaning they experienced a decrease in the size and extent of the tumor.

The median progression-free survival time — the time during which the tumor did not grow because of the medication — was 16.4 months. This data shows the best response yet seen in patients with metastatic HER2-positive breast cancer who have been heavily pretreated, Krop said. The 16 month median survival, Krop said, “is roughly double or triple … compared with typical studies in this population, where the median survival is four to five months.”

“We know, in general, drugs used in the early setting for metastatic disease are more effective,” he said. “That is why this data is so compelling. This is a very heavily pretreated population. Having new drugs in this heavily pretreated population is really helpful,” said Krop.

The medication is associated with side effects, including decreased white blood cell count, nausea, anemia, and fatigue. Moreover, some patients experienced interstitial lung disease, a serious condition that can become life-threatening.

"Interstitial lung disease is an important risk of trastuzumab deruxtecan,” Krop said. “It can be severe and requires careful monitoring and prompt intervention.” It’s unclear why the rate of interstitial lung disease was higher with trastuzumab deruxtecan than that seen with other breast cancer drugs, he said. “We need to do more research on which patients are at high risk of interstitial lung disease and how to mitigate that risk.”

The U.S. Food and Drug Administration granted priority review to trastuzumab deruxtecan in October 2019.

Other News From the SABCS

Adding Perjeta to Trastuzumab Plus Chemotherapy Reduces Recurrence

Six years of follow-up data from the phase 3 APHINITY trial showed that adding Perjeta (pertuzumab) to trastuzumab plus chemotherapy after surgery reduces the risk of cancer recurrence in women diagnosed with HER2-positive breast cancer.

The addition of the HER2 inhibitor drug trastuzumab to chemotherapy as a first-line treatment for HER2-positive, early-stage breast cancer cures many patients. But some still experience disease recurrence, said lead author of the new study Martine Piccart, MD, PhD, cofounder of Breast International Group and scientific director at the Institut Jules Bordet in Brussels.

The APHINITY trial was designed to evaluate a different HER2 inhibitor, Perjeta, to lower recurrence risk.

The study compared Perjeta added to chemotherapy plus trastuzumab, with placebo added to chemotherapy plus trastuzumab, in patients with early HER2-positive breast cancer. The results showed a benefit to patients whose cancer had spread to their lymph nodes. In that group, the addition of Perjeta resulted in a survival rate of 87.9 percent compared with 83.4 percent in the placebo group.

While the 4.5 percent improvement is modest, that result translates to more women with early-stage breast cancer who are cured, Dr. Piccart said.

“We want to cure these women,” she said, adding that any relapse results in the use of more drugs that may carry serious side effects, and lowers the chances of an ultimate cure. “The benefit that we see here is considered of significant clinical value — this 4.5 percent.”

Benefit Seen With Addition of Tucatinib in Metastatic HER2-Positive Breast Cancer

A phase 2 trial showed the investigational tyrosine kinase inhibitor drug tucatinib improved survival in patients with metastatic HER2-positive breast cancer.

The study, published simultaneously in The New England Journal of Medicine, compared tucatinib combined with the HER2 inhibitor drug trastuzumab and the chemotherapy drug Xeloda (capecitabine) with trastuzumab and Xeloda alone. The study showed progression-free survival of 33.1 percent in the tucatinib combination group compared with 12.3 percent in the placebo combination group.

Overall survival at two years was 44.9 percent in the tucatinib combination group and 26.6 percent in the placebo combination group. Almost one-half of the 612 patients in the study had brain metastasis. The study showed one-year progression-free survival of 24.9 percent in the tucatinib combination group compared with no patients with brain metastasis surviving in the placebo combination group.

Leave a comment

Your email address will not be published. Required fields are marked *