​​A Presurgery Combination Therapy May Improve Outcomes for Women With HER2-positive Breast Cancer

Excerpt:

“Results from the I-SPY 2 TRIAL show that a neoadjuvant (presurgery) therapy combination of the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla) and pertuzumab (Perjeta) was more beneficial than paclitaxel plus trastuzumab for women with HER2-positive invasive breast cancer, according to research presented here at the AACR Annual Meeting 2016, April 16-20.

“In this portion of the I-SPY2 TRIAL, the investigators tested if T-DM1 plus pertuzumab could bring a substantially greater proportion of patients to the primary endpoint of pathological complete response [pCR] compared with paclitaxel plus trastuzumab. They also examined whether this combination could meet that goal without the need for patients to receive paclitaxel. pCR is an outcome in which, following neoadjuvant therapy, no residual invasive cancer is detected in the breast tissue and lymph nodes removed during surgery.”

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TDM-1 With Docetaxel/Pertuzumab Offers Benefit in Advanced HER2-Positive Breast Cancer

Excerpt:

“Combining trastuzumab emtansine with docetaxel both with and without pertuzumab yielded promising efficacy in a phase Ib/IIa study of patients with HER2-positive locally advanced (LABC) or metastatic breast cancer (MBC). Many patients, however, required dose reductions due to toxicity.

“Trastuzumab emtansine (T-DM1) is a drug-antibody conjugate, and has been shown to offer significant survival benefits in phase III trials of HER2-positive metastatic breast cancer. ‘In preclinical studies, T-DM1 exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab,’ wrote study authors led by Miguel Martin, MD, PhD, of Hospital General Universitario Gregorio Marañón in Madrid.”

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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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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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