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…
“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.”
“Traditional neoadjuvant chemotherapy along with dual HER2-targeted blockade yielded significantly better response rates than a novel approach using HER2-targeted chemotherapy plus HER2-targeted blockade, according to a randomized phase III trial.
” ‘Despite the improvements in outcomes associated with HER2-directed therapy, approximately a quarter of patients who receive treatment for their early breast cancer remain at risk of relapse after 8–10 years, and around 15% will die within a decade,’ wrote study authors led by Sara A. Hurvitz, MD, of the David Geffen School of Medicine at the University of California, Los Angeles. A need for new strategies in this setting led the investigators to test a neoadjuvant regimen of the antibody–drug conjugate trastuzumab emtansine along with pertuzumab in comparison with traditional systemic chemotherapy along with trastuzumab plus pertuzumab.”
“A new randomized trial found that neoadjuvant trastuzumab/pertuzumab alone yields a substantially worse rate of pathologic complete response compared with trastuzumab/pertuzumab plus paclitaxel in women with early, HER2-positive, hormone receptor (HR)-negative breast cancer.
” ‘Pathologic complete response (pCR) after neoadjuvant [therapy] has strong prognostic impact in HER2 disease,’ wrote study authors led by Ulrike Nitz, MD, of the West German Study Group GmbH in Moenchengladbach, Germany. The WSG-ADAPT HER2+/HR− trial assessed whether dual blockade with trastuzumab and pertuzumab could achieve similar rates of pCR in those with strong early response to dual blockade along with chemotherapy.”
Last month, the annual American Society of Clinical Oncology (ASCO) meeting took place in Chicago. Thousands of oncologists, patients, and journalists gathered to learn about the most recent developments in cancer research and treatment. Here are some breast cancer highlights from the meeting:
Triple negative breast cancer (TNBC) is considered more responsive to treatment with immune checkpoint drugs than any other type of breast cancer. So far, these drugs have primarily been explored in metastatic TNBC, in combination with chemotherapy. The combination of “anti-PD-L1” and “anti-PD-1” immune checkpoint drugs with chemotherapy has now been examined in early-stage TNBC, in which a breast tumor can be surgically removed after neoadjuvant chemotherapy. Continue reading…
“Data from the phase II PERTAIN trial presented late last year at the 2016 San Antonio Breast Cancer Symposium (SABCS) showed that adding an aromatase inhibitor (AI) to pertuzumab (Perjeta) and trastuzumab (Herceptin) extended progression-free survival (PFS) by over 3 months versus trastuzumab plus an AI in patients with HER2-positive, HR-positive locally advanced or metastatic breast cancer.
“The median PFS was 18.89 months with the pertuzumab triplet compared with 15.80 months for trastuzumab and an AI alone (HR, 0.65; 95% CI, 0.48-0.89; P = .007). The objective response rates were 63.3% versus 55.7%, respectively.”
“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.”
“The addition of an aromatase inhibitor (AI) to pertuzumab (Perjeta) and trastuzumab (Herceptin) improved progression-free survival (PFS) by 3.09 months, when compared with trastuzumab plus an AI, according to findings from the phase II PERTAIN trial presented at the 2016 San Antonio Breast Cancer Symposium.
“In the ongoing, open-label study, the median PFS was 18.89 months with the pertuzumab combination compared with 15.80 months for trastuzumab and an AI alone. Furthermore, there was a 35% reduction in the risk of progression or death with the addition of pertuzumab (HR, 0.65; 95% CI, 0.48-0.89; P = .007).”
“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.”