“Final results from two large phase III trials confirm that the drug-antibody conjugate trastuzumab emtansine improves overall survival (OS) over other treatment options in patients with previously treated HER2-positive metastatic breast cancer. The results of the EMILIA and TH3RESA trials confirm the agent’s role in this setting.
“Trastuzumab emtansine, which links the antibody trastuzumab with the cytotoxic microtubule inhibitor DM1, was approved based on earlier results of the EMILIA study. The new analysis of that trial offers approximately twice the length of follow-up, at a median of 24.1 months.”
“Another potential drug for HER2-positive breast cancer received strong numeric support from an FDA advisory committee, tempered by reservations about a broad indication, modest clinical benefit, and toxicity issues.
“By a 12-4 vote, the Oncologic Drugs Advisory Committee (ODAC) supported FDA approval of the dual HER2/EGFR inhibitor neratinib for early HER2-positive breast cancer that relapses after trastuzumab (Herceptin) maintenance therapy.”
“Adding abemaciclib to letrozole or anastrozole improved progression-free survival (PFS) compared with either aromatase inhibitor alone in women with HR+/HER2-negative breast cancer enrolled in the phase III MONARCH 3 study, according to Eli Lilly and Company, the manufacturer of the CDK4/6 inhibitor.
“MONARCH 3 (NCT02246621) is the second phase III trial of abemaciclib to demonstrate improved PFS in patients with HR+/HER2-negative breast cancer. In March, Lilly announced that in the MONARCH 2 study, combining abemaciclib with fulvestrant extended PFS compared with fulvestrant alone in patients who had progressed during or within 1 year of receiving endocrine therapy in the neoadjuvant or adjuvant setting, or during frontline endocrine treatment for metastatic disease.”
“Over the last decade, the treatment landscape in HER2-positive breast cancer has changed dramatically, says Sara Hurvitz, MD.
” ‘I believe that a patient diagnosed today has a much greater chance of being alive 5 or 10 years from now—some of them may even be cured—and that compares very favorably with the outlook of 10 years ago when we just had 1 or 2 therapies and no evidence to support using HER2-targeted therapies after a patient’s disease grew,’ Hurvitz said.
“In an interview with Targeted Oncology, Hurvitz director of the Hematology/Oncology Breast Cancer Program and an associate professor in the Department of Medicine at the University of California, Los Angeles, discusses ongoing advances that continue to revolutionize the treatment of patients with HER2+ breast cancer.”
“Women with early-stage breast cancer and an intermediate risk recurrence score from a 21-gene expression assay may be able to avoid chemotherapy, according to a retrospective study published in Cancer.
” ‘Through years of research discoveries, it became clear that we were overtreating many women with breast cancer, especially those with early-stage breast cancer,’ Carlos H. Barcenas, MD, assistant professor of breast medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release. ‘In addition to chemotherapy’s obvious side effects, there were also long-term complications for these women as survivors.’ ”
“A cost-effectiveness analysis found that 9 weeks of trastuzumab therapy is better than the more standard 12 months in patients with HER2-positive breast cancer, without loss of clinical efficacy. The analysis is limited, though, by the need to combine various trials rather than any head-to-head comparisons.
“Trastuzumab has been shown to significantly improve survival in women with HER2-positive disease. ‘The budget impact of trastuzumab is high, mostly due to the drug’s high cost, and the most serious adverse effect observed is cardiac dysfunction,’ wrote study authors led by Caroline Clarke, PhD, of University College London in the United Kingdom. Though 12 months is considered the standard duration of therapy, some studies have also found similar results with only 9 or 10 weeks of trastuzumab.”
“In patients with hormone receptor–positive, HER2-negative, lymph node–negative breast cancer with a recurrence score (RS) based on a 21-gene expression assay of 11 to 25, outcomes were similar whether chemotherapy was used or not used, according to a retrospective analysis. However, the study’s limited follow-up means a benefit from chemotherapy in these patients cannot be ruled out.
“The Oncotype DX 21-gene expression assay is the most commonly used test of this kind in breast cancer in the United States. It offers an RS, and previous research has shown that patients with an RS below 11 fare very well when treated with endocrine therapy alone. ‘To our knowledge, it is unknown whether chemotherapy provides any additional benefit in outcomes in patients with hormone receptor–positive, HER2-negative, lymph node–negative, early-stage breast cancer with an RS of 11 to 25 who are treated with endocrine therapy,’ wrote study authors led by Carlos H. Barcenas, MD, MSc, of the University of Texas MD Anderson Cancer Center in Houston.”
“A phase I trial found that the HER2 inhibitor ONT-380 had a lower incidence of certain adverse events associated with this class of agent and notable anti-tumor activity in heavily pretreated patients with HER2-positive metastatic breast cancer (MBC).
” ‘Though existing targeted therapies are improving outcomes in patients with HER2-positive MBC, disease resistance does eventually develop in most patients,’ wrote study authors led by Stacy Moulder, MD, of the MD Anderson Cancer Center in Houston. Also, some agents preclude combination with other regimens due to off-target effects such as skin rash and diarrhea.”
“A prospective study is investigating whether breast cancer surgery can be eliminated in patients who respond well to neoadjuvant systemic therapy.
“The phase II single-center trial, conducted out of The University of Texas MD Anderson Cancer Center (NCT02945579), aims to determine how often breast cancer recurs in patients who previously received chemotherapy and follow-up radiation therapy, but not surgery, and have no evidence of disease. Forty patients with early-stage, triple-negative or HER2-positive breast cancer care underwent image-guided biopsy after completing chemotherapy and before beginning radiation therapy to see if surgery is necessary.”