“A tumor’s immune response to a single dose of the HER2 inhibitor trastuzumab predicted which patients with HER2-positive breast cancer would respond to the drug on a more long-term basis, according to the results of a study published recently in Clinical Cancer Research.
“In addition, Vinay Varadan, PhD, assistant professor at Case Western Reserve University School of Medicine and member of the Case Comprehensive Cancer Center, and his colleagues found that women with the HER2-enriched subtype of HER2-positive breast cancer—a subtype that is estrogen and progesterone receptor negative—had the highest rate of immune response to treatment with trastuzumab, with significant increases in immune response after a single dose of the drug.
“ ‘Our study showed, for the first time, that the immune-cell–activating properties of trastuzumab are likely related to the subtypes of breast cancer,’ Varadan said. ‘Knowing this can inform future trials studying the usefulness of adding immunotherapy drugs to trastuzumab.’ “
TNBC has long been considered to be more amenable to immune system-based treatments than other types of breast cancer because it is more immunogenic; that is, relatively high levels of immune cells accumulate within or adjacent to TNBC tumors. These immune cells could be triggered to attack tumors if properly activated. TNBC tumors are also likely to have a higher mutational burden (number of genetic mutations). This is one of the predictors of sensitivity to a type of treatment called immune checkpoint blockade. Drugs known as checkpoint inhibitors block the proteins PD-1 or PD-L1. In cancer, PD-L1 proteins on tumor cells bind to PD-1 proteins on immune T cells and inhibit their tumor-killing activity. Immune checkpoint drugs disable this interaction and enable activation of T cells. These drugs are actively being explored in TNBC in clinical trials.
“Among patients with HER2-positive, metastatic breast cancer that had progressed despite treatment with two or more forms of HER2-targeted therapy (trastuzumab [Herceptin] and lapatinib [Tykerb]), median overall survival was increased for those treated with trastuzumab emtansine (T-DM1 [Kadcyla]) compared with those who received treatment of physician’s choice, according to results from the phase III TH3RESA clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8–12.
“The HER2-targeted antibody-drug conjugate T-DM1 was approved by the U.S. Food and Drug Administration in February 2013 for treating patients with HER2-positive, metastatic breast cancer that had progressed after treatment with trastuzumab and a taxane.”
Erika P. Hamilton, MD, associate director, Breast Cancer and Gynecologic Cancer Research Program, principal investigator, Sarah Cannon Research Institute, on ONT-380 for HER2-positive breast cancer and the treatment’s ability to cross the blood-brain barrier. Hamilton says the reason ONT-380’s ability to cross that barrier is important is because patients with HER2-positive breast cancer have a predilection to develop brain metastases.
She added that ONT-380 was proven to be effective when combined with capecitabine (Xeloda) and trastuzumab (Herceptin), though sometimes a combination of all three proved most useful. ONT-380 is a HER2-specific inhibitor and showed promising results when tested in patients with HER2-positive breast cancer who had previously received trastuzumab and T-DM1.
In 2013, Lyndsay Sung noticed something new on the edge of her right breast. “I felt something weird—an odd thickening along the rib,” she recalls. At the time, her son was only a year old, so she thought it might have been related to breastfeeding. But then she felt it again in September 2014. Lyndsay knew she was at risk for breast cancer because her grandmother had had it, and she also knew her breasts from years of self-exams. So she went to see her family doctor. Continue reading…
“Dual HER2 blockade with trastuzumab and lapatinib was no better than trastuzumab alone in producing pathologic complete responses (pCR) in metastatic HER2-positive breast cancer patients in the neoadjuvant setting, according to a new study. Those with hormone receptor–negative disease did see an improvement with the dual blockade.
“ ‘In randomized neoadjuvant trials, dual HER2 targeting generally results in higher pCR rates, but the magnitude of this effect has varied,’ wrote study authors led by Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill. The new trial was a three-arm study of preoperative therapy in 305 patients with stage II/III HER2-positive breast cancer; 118 patients were randomized to paclitaxel along with trastuzumab and lapatinib, 120 to paclitaxel with trastuzumab alone, and another 67 to paclitaxel along with only lapatinib. That last trial arm was closed early. Results were published online ahead of print in the Journal of Clinical Oncology.”
“The use of afatinib or afatinib plus vinorelbine during or after treatment with trastuzumab, lapatinib, or both failed to show a patient benefit in women with HER2-positive breast cancer with progressive brain metastases compared with investigator’s choice of treatment, according to the results of a phase II study published in Lancet Oncology.
“Afatinib, an oral inhibitor of the ErbB family of proteins, did benefit about one-third of patients assigned to the treatment, but had no better activity than investigator’s choice of therapy, which consisted mostly of trastuzumab or lapatinib plus chemotherapy.
“ ‘No objective responses were achieved in patients treated with afatinib alone, but around one-third of patients, including those treated with afatinib alone, did not have disease progression during the first 12 weeks,’ wrote researcher Javier Cortés, MD, of Vall d’Hebron Institute of Oncology in Barcelona, and colleagues. ‘No further development of afatinib for HER2-positive breast cancer is currently planned.’ “
“Prognosis for human epidermal growth factor receptor 2 (HER2)-positive patients with lymphocyte-predominant breast cancer (LPBC) was significantly better following treatment with chemotherapy alone than it was for their counterparts receiving chemotherapy plus trastuzumab (Herceptin), an exploratory analysis of the North Central Cancer Treatment Group-N9831 trial has shown.
“Among 489 patients from the N9831 trial receiving chemotherapy alone, 10-year Kaplan-Meier estimates for recurrence-free survival (RFS) among participants with high-levels of stromal tumor-infiltrating lymphocytes (STILs) was 90.9% compared with 64.5% for patients with low-levels of STILs.
“In dramatic contrast, 10-year estimates for RFS among 456 patients who received the same chemotherapy regimen followed by weekly paclitaxel plus trastuzumab followed by trastuzumab alone were virtually identical in patients with high- and low-levels of STILs at 80% and 80.1%, respectively (HR 1.26; 95% CI 0.50-3.17; P=0.63).”
“Incidence of cardiac toxicity appeared low among patients with early HER-2–positive breast cancer who received adjuvant treatment with trastuzumab, according to results of the randomized phase 3 PHARE trial.
“Most cardiac events appeared reversible after discontinuation of trastuzumab (Herceptin, Genentech), researchers wrote.
“The French National Cancer Institute sponsored the PHARE trial, which included 3,380 patients with early HER-2–positive breast cancer randomly assigned 1:1 to the standard 12-month trastuzumab regimen or a 6-month regimen.”