“Brain metastases from primary breast cancer tumors often acquire clinically actionable genetic alterations, according to a small study. About one fifth of ERBB2/HER2-negative cases switched to HER2-positivity in the brain metastases.
” ‘Limited therapeutic options exist for patients with brain metastases,’ wrote study authors led by Nolan Priedigkeit, BS, of the University of Pittsburgh. ‘ERBB2/HER2-positive brain metastases have demonstrated encouraging responses to ERBB2/HER2-targeted therapies in recent clinical trials.’ ERBB2/HER2-negative brain metastases, however, have shown no such response.”
University of Colorado Cancer Center | Jan 10, 2017
“Phase 1 clinical trial data published this week in the journal Clinical Cancer Research show early promise of the investigational anti-cancer agent tucatinib (formerly ONT-380) against HER2+ breast cancer. The 50 women treated had progressed despite a median 5 previous treatment regimens. Twenty-seven percent of these heavily pretreated patients saw clinical benefit from the drug, with at least ‘stable disease’ at 24 or more weeks after the start of treatment. These data have led to two subsequent Phase Ib studies, resulting in tucatinib earning FDA fast-track status and the expansion of this study once meant only to demonstrate drug safety into the “pivotal” trial that will determine approval.”
“Deregulation and inhibition of the immune system contributes to cancer development. Many therapeutic strategies aim to re-stimulate the immune system to recognize cancer cells and target them for destruction. Researchers from Moffitt Cancer Center report that a dendritic cell vaccine that targets the HER2 protein on breast cancer cells is safe and effectively stimulates the immune system leading to regression of early-stage breast cancer.”
“Immunotherapy is a fast growing area of cancer research. It involves developing therapies that use a patient’s own immune system to fight and kill cancer. Moffitt Cancer Center is working on a new vaccine that would help early-stage breast cancer patients who have HER2 positive disease.
“The HER2 protein is overexpressed in nearly 25 percent of all breast cancer tumors and is associated with aggressive disease and poor prognosis. Moffitt researchers, led by physician-scientist Brian J. Czerniecki, M.D., Ph.D., have previously shown that immune cells are less able to recognize and target cancer cells that express HER2 as breast cancer progresses into a more advanced and invasive stage. This suggests that strategies that can restimulate the immune system to recognize and target HER2 early during cancer development may be effective treatment options.”
“Adding a drug to a standard regimen for hormone receptor (HR)-positive and HER2-positive breast cancer improved progression-free survival, a researcher said here.
“In a Phase II randomized trial, investigators compared an aromatase inhibitor (AI) combined with pertuzumab (Perjeta) and trastuzumab (Herceptin) versus an AI just with trastuzumab in women with locally advanced or metastatic breast cancer, Grazia Arpino, MD, PhD, of the University of Naples Federico II in Italy, reported at a general session at the San Antonio Breast Cancer Symposium.
“The three-drug combination led to a median of 18.89 months without progression, compared with 15.8 months for the two drugs.”
“Breast cancer patients sometimes end up dying when their tumors spread all the way to the brain. Some very good drugs already exist for patients with breast cancer, especially ones with tumors that overexpress the HER2 marker, but that success has raised a new question: Can drugmakers take another step, and fight those deadly brain metastases that get people in the end?
“Seattle-based Cascadian Therapeutics is testing that idea this week with researchers gathered at the San Antonio Breast Cancer Symposium. Cascadian is reporting today that patients who got conventional capecitabine and trastuzumab, plus an experimental small-molecule drug, tucatinib (aka ONT-380), lived a median of 7.8 months without their tumors getting worse. About 61% of patients on that triple-drug combo saw tumors shrink. It’s an impressive result, given that these patients were especially ill when they enrolled in the study, having already received a median of three prior rounds of HER2-targeted therapy. The data are also holding up over time: a snapshot of the data from June showed patients living a median of 6.3 months without their tumors spreading.”
“A novel HER2-targeting antibody-drug conjugate showed promising antitumor activity across multiple tumor types, including HER2-postive breast cancer, according to phase I data presented at the 2016 ESMO Congress.
” ‘Antibody-drug conjugates represent promising drugs with a wider therapeutic window by effecting efficient and specific drug delivery to oncogene expressing tumor cells,’ explained lead author Kenji Tamura, MD, PhD, chairman, Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.”
“The FDA has granted priority review designation to a new drug application (NDA) for ribociclib (LEE011) for use in combination with letrozole as a frontline therapy for patients with hormone-receptor (HR)–positive, HER2-negative advanced breast cancer.
“The NDA for the CDK 4/6 inhibitor is primarily based on findings from the phase III MONALEESA-2 trial, in which combining ribociclib with letrozole reduced the risk of progression or death by 44% compared with letrozole alone in the first-line setting for HR+/HER2- advanced breast cancer (HR, 0.556; 95% CI, 0.43-0.72; P = .00000329). Under the priority designation, the NDA will be reviewed within 6 months, compared with the standard 10-month review.”
“Results from the KRISTINEand NSABP B-41 trials provided the latest data on the use of pertuzumab (Perjeta), trastuzumab (Herceptin), ado-trastuzumab emtansine (T-DM1; Kadcyla), and lapatinib (Tykerb) for the neoadjuvant treatment of patients with HER2-positive breast cancer.
“In a lecture at the 2016 ASCO Annual Meeting, Stephen K. Chia, MD, an assistant professor in the division of Medical Oncology at the University of British Columbia, highlighted the key findings from these trials and their implications for the treatment of HER2+ breast cancer.”