Twenty years ago, no targeted treatments existed for breast cancers with high levels of a protein called HER2 (HER2-positive, or HER2+). The significance of HER2 in breast cancer had only been recognized in 1987, when excessive levels of the protein were identified in about 20% of breast cancers. Oncologists realized that high levels of HER2 mark a type of cancer with a poor prognosis, as compared to the predominant type of breast cancer: estrogen receptor-positive, HER2 negative (HER2-).
The possibility of targeting HER2 to treat cancer was fulfilled in 1998, when the U.S. Food and Drug Administration (FDA) approved Herceptin (generic name trastuzumab), for treatment of metastatic HER2+ breast cancer. Made by Genentech, Herceptin is a type of drug known as a humanized antibody, meaning that it mimics an immune system attack on tumor cells, specifically those with high levels of HER2. Now, 20 years later, it is easier to appreciate the significance of this drug, which literally changed the lives of many HER2+ breast cancer patients, and continues to do so today. Continue reading…
“Adding to a growing list of similar results, the Short-HER study was unable to show noninferiority of 9 weeks of trastuzumab compared with the standard 1 year when given along with chemotherapy in women with HER2-positive breast cancer. Shorter administration does, however, reduce the risk of cardiotoxicity.
” ‘Adjuvant pivotal trials with 1-year trastuzumab have significantly improved the prognosis of HER2-positive early breast cancer,’ wrote study authors led by Pierfranco Conte, MD, of the Istituto Oncologico Veneto in Italy. Several studies have attempted to reduce the duration of trastuzumab, though most have failed to show noninferiority.”
“Outcomes for patients with HER2-positive breast cancer did not differ when treated with sequential chemotherapy plus trastuzumab compared with a concurrent approach, according to a new phase III trial.
” ‘The effectiveness of trastuzumab with chemotherapy in the neoadjuvant setting is evident; however, the cardiac safety of trastuzumab combined with anthracyclines has been questioned,’ wrote study authors led by Kelly K. Hunt, MD, of the University of Texas MD Anderson Cancer Center in Houston.”
“The combination of neratinib (Nerlynx) and T-DM1 (ado-trastuzumab emtansine; Kadcyla) induced an overall response rate of 60% in previously-treated women with HER2-positive metastatic breast cancer, according to results from the phase Ib NSABP FB-10 study presented at the 2018 ASCO Annual Meeting.
“Among 12 of 20 evaluable patients with objective responses, 3 had a complete response and 9 had a partial response. An additional 2 patients had stable disease, and 6 patients had progressive disease.”
“Tucatinib used in combination with capecitabine, trastuzumab (Herceptin), or both agents showed promising antitumor activity in heavily pretreated women with HER2-positive breast cancer with or without brain metastases, according to findings published in The Lancet Oncology.
“In phase Ib results from a nonrandomized, open-label study, 83% (5/6) of patients with measurable disease treated with tucatinib/capecitabine had an objective response, as did 40% (6/15) of patients receiving tucatinib/trastuzumab. Sixty-one percent (14/23) of patients treated with the combination of all 3 drugs had an objective response.”
“A combined approach targeting estrogen receptor (ER), HER2, and RB1 yielded promising results in terms of Ki-67 expression in an exploratory study of women with HER2-positive, ER-positive breast cancer.
” ‘HER2-positive, ER-positive tumors have molecular features distinct from those of HER2-positive, ER-negative cancers, suggesting that the two types of tumors should be treated with differently tailored approaches,’ wrote study authors led by Luca Gianni, MD, of San Raffaele Scientific Institute in Milan. Previous work has suggested that a combined approach targeting HER2, ER, and RB1 may improve outcomes.”
“The adjuvant treatment landscape for patients with HER2-positive breast cancer continues to grow, particularly following the recent FDA approval of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy, which was based on findings from the APHINITY trial.
“In the phase III trial, the combination demonstrated a 3-year invasive disease-free survival (DFS) rate of 94.1%, which represented an 18% reduction in the risk of developing invasive disease or death. The benefit was more pronounced among higher-risk patients. The DFS rate for patients with node-positive disease was 92.0% with pertuzumab versus 90.2% with standard therapy.”
“A combination of pembrolizumab (Keytruda) and trastuzumab, tested in patients with trastuzumab-resistant advanced HER2-positive breast cancer, was well tolerated and had clinical benefit in patients whose tumors were positive for a biomarker for pembrolizumab, according to data presented from the phase Ib/II PANACEA trial at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.
“ ‘We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab,’ said Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG).”