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.”


The Coming Third Wave of Precision Cancer Medicines

“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 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.”


Anti-HER2 Therapy After WBRT Increases Survival in Brain Mets Patients

“Both chemotherapy and anti–human epidermal growth factor receptor 2 (HER2) therapy can improve survival outcomes in HER2-positive breast cancer patients with brain metastases who undergo whole-brain radiotherapy (WBRT), according to a new retrospective study.

“ ‘The incidence of brain metastases is higher in HER2-positive breast cancer compared with other breast cancer patients,’ wrote study authors led by Jiayi Chen, MD, of Shanghai Cancer Center at Fudan University in China. ‘Although adjuvant trastuzumab could not effectively prevent brain metastases, recent studies demonstrated a significant survival benefit of salvage trastuzumab-based therapy for these patients.’

“In the study, the authors retrospectively analyzed 60 patients with HER2-positive breast cancer and brain metastases who underwent WBRT to examine the benefits of various systemic therapies in this setting. The results were published in Breast Cancer.”


Roche's Perjeta Regimen Approved in Europe for Use Before Surgery in Early Stage Aggressive Breast Cancer

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission (EC) has approved the use of Perjeta® (pertuzumab) in combination with Herceptin® (trastuzumab) and chemotherapy for the neoadjuvant treatment (use before surgery) of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence. The Perjeta regimen is the first neoadjuvant breast cancer treatment approved by the EC based on pCR data.

“Every year in Europe nearly 100,000 people are diagnosed with HER2-positive breast cancer, an aggressive type of the disease that is more likely to progress than HER2-negative cancer.1,2 Treating people with breast cancer early, before the cancer has spread, may improve the chance of preventing the disease from returning. Neoadjuvant treatment is given before surgery and is aimed at reducing tumour size so it is easier to surgically remove. pCR is achieved when there is no tumour tissue detectable at the time of surgery in the affected breast or in the affected breast and local lymph nodes. It is a common measure of neoadjuvant treatment effect in breast cancer and it can be assessed more quickly than traditional endpoints in eBC.

“ ‘Today’s approval is a significant milestone in the neoadjuvant treatment of HER2-positive early breast cancer, bringing Perjeta to patients years earlier than typical adjuvant treatment,’ said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. ‘We are committed to making the Perjeta regimen available to appropriate patients in the EU as early as possible.’ “


Drug Combo Effective for Metastatic HER2+ Breast Ca

“The combination of lapatinib (Tykerb) and trastuzumab (Herceptin) is active and well-tolerated when given to patients with human epidermal growth factor receptor 2-positive (HER2) metastatic breast cancer (MBC) who have received up to two lines of therapy for advanced disease, a nonrandomized phase II study now shows.

“What’s more, early metabolic imaging by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) appears to provide the key to selecting patients who can be treated with targeted regimens and spared the toxicity of chemotherapy, Nancy U. Lin, MD, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, Ma., and colleagues report online in the Journal of Clinical Oncology.

” ‘Because the number of treatment options and their cost for patients with HER2-positive breast cancer continues to increase, a key question is how best to tailor therapies to individual patients,’ said Lin. ‘In the metastatic setting, predictive tests for clinical benefit could spare patients unnecessary toxicity and cost from ineffective therapies and maximize the likelihood of meaningful improvements from treatment. In the early-stage setting, predictive tests may reduce both under- and overtreatment.’ “


Adding Everolimus to First-Line Trastuzumab-Paclitaxel Does Not Increase Progression-Free Survival in HER2-Positive Breast Cancer

“In the phase III BOLERO-1 trial, reported in The Lancet Oncology, Hurvitz et al found that the addition of the mTOR inhibitor everolimus (Afinitor) to trastuzumab (Herceptin)-paclitaxel did not significantly increase progression-free survival among patients with HER2-positive advanced breast cancer. A 7-month prolongation in progression-free survival was observed with everolimus among patients with hormone receptor–negative disease.”


Higher Tumor-Infiltrating Lymphocyte Level Associated With Better Outcomes in HER2-Positive Early Breast Cancer Independent of Neoadjuvant Treatment

“In an analysis of the NeoALTTO trial reported in JAMA Oncology, Salgado et al found that a higher level of tumor-infiltrating lymphocytes was associated with improved pathologic compete response rate and event-free survival independent of neoadjuvant treatment received in patients with HER2-positive early breast cancer.

“In NeoALTTO, 455 patients were randomly assigned to receive neoadjuvant trastuzumab (Herceptin), lapatinib (Tykerb), or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks and three cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. Percentage of tumor-infiltrating lymphocytes were measured by hematoxylin-eosin stained core biopsy sections taken at diagnosis.”


Study: Breast Ca Patients Need Better Cardiac Monitoring

“Breast cancer patients received suboptimal cardiac monitoring during treatment with trastuzumab (Herceptin), according to a large population-based study.

“Among more than 2,000 patients, only 36% of evaluable participants received adequate monitoring for cardiotoxicity in accordance with current guidelines, reported Mariana Chavez-MacGregor, MD, of the MD Anderson Cancer Center in Houston, and colleagues.

“Interestingly, physician characteristics had more influence than patient factors on cardiac monitoring, they wrote in the Journal of Clinical Oncology

” ‘We suspected that the rates of cardiac monitoring were going to be low, but we were surprised on how low, particularly in this high-risk group of patients,’ Chavez-MacGregor, a medical oncologist, told MedPage Today in a separate interview. ‘Of particular concern was that even among patients with cardiac comorbidities the rates of cardiac monitoring were not higher.’ “


High TIL Levels Predict Positive Outcomes in HER-2–Positive Breast Cancer

“High levels of tumor-infiltrating lymphocytes served as an independent positive predictive marker for EFS and pathological complete response in HER-2–positive early breast cancer treated with chemotherapy and anti-HER–2 agents, according a secondary analysis of the NeoALTTO trial.

“ ‘Increasingly, oncogenic addiction, in which tumors become dependent on a sole oncogenic pathway for growth, is thought to promote a tumor microenvironment conducive to immune escape,’ Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne, and colleagues wrote. ‘Although this had not been shown yet for HER-2 oncogenic signaling, one could speculate that anti-HER–2 therapy may not only work in a cell-intrinsic manner but may also reserve HER-2–induced immunosuppression as a mechanism for action.’

“The NeoALTTO trial included 455 women with HER-2–positive early-stage breast cancer between 2008 and 2010. The researchers randomly assigned patients to neoadjuvant treatment with trastuzumab (Herceptin, Genentech), lapatinib (Tykerb, GlaxoSmithKline) or both.

“Patients received the initial treatment for 6 weeks, followed by weekly paclitaxel for 12 weeks and three treatment cycles of fluorouracil, epirubicin and cyclophosphamide after surgery.”