“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.”
“Though the addition of pertuzumab to docetaxel and trastuzumab as first-line therapy for HER2-positive breast cancer has been shown to yield a substantial survival benefit, a new analysis shows that there is very little chance that pertuzumab would be cost effective in the United States.
“The CLEOPATRA trial showed that pertuzumab along with docetaxel and trastuzumab (THP) resulted in a median survival in HER2-positive metastatic breast cancer patients of 56.5 months, compared with only 40.8 months for the latter two drugs alone (TH). ‘These exceptional results come at a price,’ wrote researchers led by Ben Y. Durkee, MD, PhD, of Stanford University in California. ‘Our work shows that an insurer could expect to pay $4,649 per week for the THP regimen at Medicare rates. Private contractors and smaller entities would pay more.’
“The researchers used a decision-analytic Markov model to evaluate the regimen’s cost effectiveness, based on the study population from CLEOPATRA and the assumed number of patients for whom the THP regimen would be recommended in the metastatic setting. Results were published online ahead of print in the Journal of Clinical Oncology.”
“Targeted treatments for cancer have been extending and saving lives for more than 15 years—precision medicine isn’t a new idea in oncology. Now drugs pioneered on select, specific cancers are, one by one, finding new applications.
“The first wave of targeted drug approvals were for cancers associated with specific mutations. Herceptin (traztuzumab) led the way, approved in 1998. It’s a monoclonal antibody deployed against the HER2/neu receptor that is overabundant in some aggressive and early-onset breast cancers. Robert Bazell’s excellent book Her 2 tells the tale.
“In 2001 came the blockbuster Gleevec (imatinib), a small molecule tyrosine kinase inhibitor that intercepts signals to divide. Erin Zammett’s My So-Called Normal Life with Cancer relates that story. A very young editor at Glamour magazine when a routine check-up revealed chronic myelogenous leukemia, Erin’s recovery was one of the first of thousands thanks to this now famous drug.”