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HER2-Positive Breast Cancer Study Finds New Option to Avoid Cardiac Toxicity

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A new study found no differences in long-term outcomes associated with 2 different approaches to administering trastuzumab (Herceptin) with neoadjuvant chemotherapy in patients with HER2-positive breast cancer. Receiving the combination sequentially rather than concurrently eliminates the known cardiac toxicities associated when chemotherapy and HER2 therapy are given at the same time, researchers said.

A new study found no differences in long-term outcomes associated with 2 different approaches to administering trastuzumab (Herceptin) with neoadjuvant chemotherapy in patients with HER2-positive breast cancer. The study was led by the MD Anderson Cancer Center at the University of Texas and published in in JAMA Oncology.

The new research is follow-up to a phase 3 MD Anderson-led study that found these patients also can achieve a high pathological complete response (pCR), or no evidence of disease at the time of surgery, when the same therapy regimen is given sequentially, according to a statement from MD Anderson.

Receiving the combination sequentially rather than concurrently eliminates the known cardiac toxicities associated when chemotherapy and HER2 therapy are given at the same time.

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The study of 280 patients revealed no difference in disease-free survival (DFS) or overall survival (OS) for patients given a regimen of paclitaxel plus trastuzumab followed by fluorouracil, epirubicin, and cyclophosphamide (FEC) plus trastuzumab, compared with a regimen of FEC followed by paclitaxel plus trastuzumab.

Across a median follow-up of 5 years, no differences were found in DFS or OS between the 2 approaches. The phase 3 study was conducted through the American College of Surgeons Oncology Group, now the Alliance for Clinical Trials in Oncology.

“Our findings from both studies allow for all women with this class of breast cancer to be spared of cardiotoxicities associated with anthracycline and trastuzumab given at the same time,” said Kelly Hunt, MD, professor and chair, breast surgical oncology, and the study’s corresponding author. “The research also offers physicians definitive clinical guidance. Many have opted to treat with a more aggressive approach because the patient’s disease was a higher stage, or because of the woman’s young age. Our study confirms that for HER2+ breast cancer patients, less is more.”

The randomized phase 3 trial enrolled 280 women with operable HER2-positive invasive breast cancer at 36 centers across the country from September 2007 through December 2011. Therapy was followed by surgery.

The sequential arm (arm 1) enrolled 138 patients who received the 3-drug chemotherapy combination regimen known as FEC on day 1 of a 21-day cycle for 4 cycles, followed by paclitaxel plus trastuzumab weekly for 12 weeks.

The concurrent arm (arm 2) enrolled 142 patients who received paclitaxel plus trastuzumab weekly for 12 weeks, followed by FEC on day 1 of a 21-day cycle and trastuzumab on days 1, 8 and 15 of the 21-day cycle for 4 cycles.

All patients enrolled received trastuzumab therapy for 1 year. Women with hormone receptor—positive tumors received endocrine therapy. Patients underwent radiation at their physician’s discretion.

The trial’s primary end point was the pCR rate in the breast. Secondary end points were the pCR rate in the lymph nodes, DFS, and OS. The researchers previously reported no difference in pCR rates between the 2 arms.

In this study, they found no difference in either DFS or OS rates with concurrent or sequential delivery. In arm 1, 18 women had their cancer recur and 2 were diagnosed with secondary cancers; 22 recurrences and 3 secondary cancers were diagnosed in arm 2.

Given the many anti-HER2 treatment options available, the extended OS on trastuzumab should have important clinical and financial implications, the authors said.

“Nationally, the trend is to give patients more than one type of anti-HER2 treatment upfront before their surgery. There are now multiple options approved to treat women with HER2+ disease, but with significant toxicity and financial costs,” said Aman Buzdar, MD, vice president, clinical research, and the lead author on the pCR study findings.

Buzdar and Hunt said the majority of patients with HER2-positive breast cancer are still having surgery first, despite more than half of patients achieving a pCR with neoadjuvant therapy.

“The best way to determine whose cancer is sensitive to therapy is to give it when the cancer is intact. We need to focus on offering additional treatments to patients who still have persistent disease at surgery, thereby avoiding unnecessary costs and toxicities,” said Hunt.

Reference

Buzdar AU, Suman VS, Meric-Bernstam F, et al. Disease-free and overall survival among patients with operable HER2-positive breast cancer treated with sequential vs concurrent chemotherapy-the ACOSOG Z1041 (Alliance) randomized clinical trial [published online September 6, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.3691.

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