Neoadjuvant HER2+ Breast Cancer Options Need Refinement, Expert Says

Excerpt:

“While recent findings from the I-SPY 2 trial have shown potential with the combination of ado-trastuzumab emtansine (T-DM1; Kadcyla) and pertuzumab (Perjeta) for patients with HER2-positive breast cancer, the neoadjuvant space still has a lot of work ahead, according to Lisa A. Carey, MD.

“Results presented at the 2016 AACR Annual Meeting1 showed that, out of the 249 patients enrolled on the I-SPY 2 study, 54% of those who received T-DM1/pertuzumab experienced a pathological complete response (pCR) rate compared with 22% of those who received the combination of paclitaxel (Abraxane) plus trastuzumab (Herceptin).

“This suggests that T-DM1 could increase overall survival (OS) in this patient population, but Carey adds more research with the regimen needs to be conducted.”

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Neratinib Plus Paclitaxel vs. Trastuzumab Plus Paclitaxel in Breast Cancer

Excerpt:

“While neratinib plus paclitaxel was not superior to trastuzumab plus paclitaxel as first-line treatment for ERBB2-positive metastatic breast cancer in terms of progression-free survival, the combination was associated with delayed onset and reduced frequency of central nervous system metastases, a finding that requires a larger study to confirm, according to an article published online by JAMA Oncology.

“Metastatic ERBB2-positive breast cancer has a characteristic spread with most patients developing liver metastases and about half having poor prognosis with central nervous system involvement.

“Ahmad Awada, M.D., of the Jules Bordet Institute, Brussels, and coauthors conducted a randomized clinical trial to examine progression-free survival in women with recurrent or metastatic ERBB2-positive breast cancer. They also examined secondary outcomes that included time to symptomatic or progressive central nervous system lesions and safety.”

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EBCC-10 NEWS: Combination of Lapatinib and Trastuzumab Shrinks HER2 Positive Breast Cancer Significantly in 11 Days After Diagnosis

“Amsterdam, The Netherlands: Approximately a quarter of women with HER2 positive breast cancer, who were treated with a combination of the targeted drugs lapatinib and trastuzumab before surgery and chemotherapy, saw their tumours shrink significantly or even disappear, according to results from a clinical trial.

“Professor Nigel Bundred told the 10th European Breast Cancer Conference (EBCC-10) today (Thursday): ‘This has ground-breaking potential because it allows us to identify a group of patients who, within 11 days, have had their tumours disappear with anti-HER2 therapy alone and who potentially may not require subsequent chemotherapy. This offers the opportunity to tailor treatment for each individual woman.’

“Prof Bundred, who is Professor of Surgical Oncology at The University of Manchester and the University Hospital of South Manchester NHS Foundation Trust (UK), was presenting results from the UK EPHOS-B multi-centre, clinical trial, in which 257 women with newly-diagnosed, operable, HER2 positive disease were recruited between November 2010 and September 2015.”


Single Dose of Trastuzumab Kick Starts Immune Response in Certain Breast Cancers

“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.’ “


Putting Immune Checkpoint Blockade to the Test in Breast Cancer


About 10 months ago, we asked: Is There a Future for Immunotherapy in Breast Cancer? Now, we can answer this question with a qualified “yes.” The data show why:

Triple-negative breast cancer (TNBC)

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.

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Drugs Prevent Heart Damage during Breast Cancer Treatment, Study Shows

“Heart medication taken in combination with chemotherapy reduces the risk of serious cardiovascular damage in patients with early-stage breast cancer, according to results from a new landmark clinical trial.

“Existing research has shown some cancer therapies such as Herceptin greatly improve survival rates for , but come with a fivefold risk of heart failure—a devastating condition as life-threatening as the cancer itself.

“A new five-year study, led by researchers at the University of Alberta and Alberta Health Services and funded by the Canadian Institutes for Health Research (CIHR) and Alberta Cancer Foundation, shows that two kinds of heart medications, beta blockers and ACE inhibitors, effectively prevent a drop in heart function from cancer treatment.”


T-DM1 Improved Overall Survival for Heavily Pretreated Patients With HER2-positive Breast Cancer

“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.”


Video: Dr. Erika P. Hamilton on ONT-380 in HER2-Positive Breast Cancer Patients With Brain Metastases

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.

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Super Patient: Lyndsay Sung Catches Her Breast Cancer Just In Time


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…