Studies at ASCO Focus on HER2-Positive Breast Cancer
During the Monday afternoon presentations, researchers discussed promising treatments for HER2-positive breast cancers and ER/HER2-positive disease
Researchers reported findings from several studies focusing on HER2-positive breast cancer during the American Society of Clinical Oncology's annual meeting. The studies focused on an oral therapy, neratinib, being studied in early-stage and metastatic breast cancer, as well as different ways to treat breast cancer that is both HER2- and hormone-positive.
Neratinib is a kind of medicine called a tyrosine kinase inhibitor. It has been shown to stop disease from growing in HER2-positive metastatic breast cancer that does not respond to trastuzumab (Herceptin). Researchers with the ExteNet study wanted to learn if neratinib could also be helpful in stopping recurrence in early-stage, HER2-positive breast cancer.
Study participants who had already been treated with trastuzumab and chemotherapy were given 12 months of either a neratinib pill or a placebo (sugar) pill. Researchers then compared invasive disease-free survival (IDFS), the length of time after breast cancer treatment that a person lives with no sign of invasive disease, in the two groups.
Lead researcher Arlene Chan, MD, of the Breast Cancer Research Centre at Western Australia and Curtin University, in Australia, reported that participants who took neratinib had a small but statistically significant increase in IDFS. This means the difference was less likely to have happened because of chance. After 2 years, 91.6 percent of participants in the placebo group had not developed invasive breast cancer, versus 93.9 percent of participants in the neratinib group. The benefit was greatest in participants who also had hormone-positive disease.
In general, people who took neratinib had few side effects, but almost all participants had diarrhea.
Researchers plan to continue following these participants, in order to look at 5-year IDFS rates and overall survival.
In a review of the HER2 presentations on Tuesday morning, Eric Winer, MD, chief of the division of women’s cancers at Dana-Farber Cancer Institute in Boston called the results interesting but cautioned that the follow-up time of less than 1 year means neratinib is not ready to be offered today to people with early-stage disease. It should continue to be studied, especially in people with HER2 and ER-positive disease, he said.
T-DM1, or ado-trastuzumab emtansine (Kadcyla), is FDA approved for treatment of metastatic, HER2-positive breast cancer that has grown despite other HER2-targeting treatments. Researchers with the MARIANNE trial wanted to know if T-DM1 could be an option as a person’s first treatment for metastatic disease.
Trial participants received either T-DM1 plus placebo, T-DM1 plus the anti-HER2 targeted therapy pertuzumab(Perjeta), or the standard treatment, trastuzumab plus chemotherapy. Researchers were interested in progression-free survival (PFS), the time between starting treatment and the disease growing.
Lead researcher Paul Anthony Ellis, MD, of Guy’s Hospital and the Sarah Cannon Research Institute, in the United Kingdom, reported that in this trial, T-DM1 worked as well as the standard treatment but it did not work significantly better. PFS was 13.7 months in the standard treatment group, 14.1 in the T-DM1 alone group, and 15.2 in the T-DM1 plus pertuzumab group.
Because neither of the study treatments worked better than the standard treatment, Dr. Ellis said trastuzumab plus chemotherapy should for now remain the recommended first treatment for newly diagnosed metastatic HER2-positive breast cancer.
Early results of the phase III MARIANNE trial were announced at the end of 2014. For more information, see our past coverage.
Breast cancer can be hormone receptor-positive, meaning it grows in the presence of the hormones estrogen, progesterone, or both. It can also be HER2-positive, meaning it grows because of too many human epidermal growth factor receptor 2 proteins on breast cells. When breast cancer is both hormone receptor-positive and HER2-positive, it is sometimes called triple-positive.
Right now, the current standard treatment for people with ER/HER2-positive breast cancer is HER2- and hormone-targeting therapy plus chemotherapy. But early research suggests triple-positive breast cancer may behave differently than either HER2-positive or hormone-positive breast cancer does alone.
Researchers with the ADAPT trial wanted to learn more about ER/HER2-positive breast cancer, with the goal that we may someday be able to offer targeted therapy without chemotherapy to some people with triple-positive disease. To study this issue, they gave 380 participants 12 weeks of neoadjuvant, or pre-surgery, therapy:
- The first group received the HER2-targeted therapy TDM-1 and a hormonal therapy, either tamoxifen (for premenopausal women) or an aromatase inhibitor (for postmenopausal women).
- The second group received only the HER2-targeted therapy TDM-1.
- The third group received the HER2-targeted therapy trastuzumab (Herceptin) and a hormonal therapy, either tamoxifen or an aromatase inhibitor. This was the control group, because participants received the approved standard therapy.
After surgery, everyone received treatment with the chemotherapy medicine paclitaxel (Taxol), as well as additional trastuzumab and hormonal therapy. The researchers compared the groups for pathologic complete response (pCR), or whether invasive cancer can no longer be found in the breast and lymph nodes after treatment.
Lead researcher Nadia Harbeck, MD, of the University of Cologne, in Germany, reported that the rate of pCR was 45.8 and 40.5 percent in the two groups that received T-DM1, but just 6.7 percent in the group that received standard treatment. She also reported that adding hormonal therapy to T-DM1 had a statistically significant benefit in premenopausal women, but not in postmenopausal women.
The number of premenopausal women in the study was small, but the findings by menopausal status are a “very important issue to follow up” in future studies, Dr. Harbeck said.
Check out our previous coverage of ASCO 2015, including studies on surgery and preventing hair loss, hormone receptor-positive breast cancer, and triple-negative disease. Don’t forget to join us for our annual ASCO webinar on Thursday, June 4.