HER2-Enriched Molecular Subgroup Highly Sensitive to Breast Cancer Regimens

“The primary analysis of the phase III CALGB 40601 trial found that pathologic complete response (pCR) to dual HER2 blockade was not statistically higher than anti-HER2 monotherapy. However, there was a high level of intertumoral heterogeneity, and patients with the HER2-enriched subtype had a high pCR with both single and dual anti-HER2 therapy, according to data recently published in the Journal of Clinical Oncology.

“ ‘This trial paves the way for integrating molecular analyses into other trials in HER2-positive breast cancer, and may allow us to take a less-is-more approach for women who are selected to be highly sensitive to targeted treatments and to have a good prognosis,’ said lead study author Lisa Carey, MD, a UNC Lineberger member, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research at the University of North Carolina School of Medicine, and the physician-in-chief of the North Carolina Cancer Hospital, in a statement.”


Dual HER2 Blockade Fails to Improve Response Rate in HER2-Positive Breast Cancer

“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.”


No Benefit to Afatinib in HER2-Positive Breast Cancer With Brain Metastases

“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.’ “


To Type or to Print? Oncotype DX and Mamma/BluePrint Tests for Breast Cancer


Women diagnosed with localized breast cancer face difficult decisions with their doctors. What kind of neoadjuvant (before surgery) treatment to choose? Should chemotherapy follow surgery? Based on the subtype of breast cancer, should specific chemotherapy drugs be used? Continue reading…


HER2-Positive Breast CA Patients Prosper on Solo Chemo

“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).”


ESMO Commentary: Preliminary Results from PERUSE Study Increase Treatment Options in HER-Positive Patients with Metastatic Breast Cancer

Preliminary safety results from the PERUSE study presented at the European Cancer Congress 2015 (ECC 2015) in Vienna, Austria, open the door for the taxanes nab-paclitaxel and paclitaxel to be used in HER2-positive patients with metastatic breast cancer.

“ ‘Therapy in HER2-positive metastatic breast cancer has been influenced by the CLEOPATRA trial, which led to the registration of pertuzumab and trastuzumab in the first line setting,’ said Professor Jens Huober, Head of the Breast Centre at the University of Ulm, Germany who has shared his views on new steps forward in the treatment of this subset of patients. ‘The CLEOPATRA trial used only docetaxel,’ he added.

“ ‘With PERUSE we now know that at least in terms of safety and tolerability we have good alternatives to docetaxel, namely nab-paclitaxel and paclitaxel, which for the majority of patients are probably less toxic,’ he said.”


Cardiac Toxicity Low Among Patients Treated with Adjuvant Trastuzumab

“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.

“Trastuzumab improves outcomes for women with early HER-2–positive breast cancer, but prior studies have shown cardiotoxicity rates between 2% and 7%.

“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.”


Case Study Shows Early Efficacy for Neratinib in HER2-Mutated Metastatic Breast Cancer

“Treatment with the second-generation HER2/EGFR-targeted TKI neratinib resulted in a partial response and dramatic improvement in functional status for a patient with HER2-mutated breast cancer, according to a single-patient case study published in the Journal of the National Comprehensive Cancer Network.

” ‘The treatment of this patient is an excellent example of collaboration between basic research, clinical application and biotechnology companies for the benefit of patients,’ co-author of the publication Noa Efrat Ben-Baruch, MD, head of the Department of Oncology, Kaplan Medical Center, Rehovot, Israel, said in a statement. ‘With the advent of molecular profiling of patients with metastatic disease, such collaborations are of utmost importance for the development of new drug candidates outside of formal clinical trials.’

“According to the authors of the study, these findings represent the first successful single-agent treatment for patients with breast cancer harboring an activating mutation in the HER2 tyrosine kinase. In most situations, HER2 tyrosine kinase mutations occur independently from HER2 gene amplifications, making these patients ineligible or unlikely to respond to traditional HER2-targeted therapies.”


Pertuzumab Not Cost Effective in Metastatic HER2-Positive Breast Cancer

“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.”