NEW YORK (Reuters Health) – In the neoadjuvant treatment of HER2-positive breast cancer, administering trastuzumab concurrently with anthracyclines offers no advantage over sequential administration, according to the results of a new multicenter trial.

The researchers compared the two approaches to neoadjuvant therapy in 282 women with operable HER2-positive invasive breast cancer. The participants underwent surgery within 6 weeks after completing treatment.

Those randomly assigned to sequential neoadjuvant treatment received fluorouracil, epirubicin, and cyclophosphamide (FEC) for four cycles, followed by paclitaxel and trastuzumab weekly for 12 weeks.  The concurrent treatment group received paclitaxel and trastuzumab for 12 weeks followed by four FEC cycle plus weekly trastuzumab.

The pathological complete response rate was 56.5% in the sequential treatment group compared to 54.2% in the concurrent treatment group, Dr. Kelly K. Hunt, at the University of Texas MD Anderson Cancer Center in Houston, and colleagues found.

Rates of neutropenia were 25.3% and 31.7% in the two groups, respectively, according to the report in The Lancet Oncology online November 13.

While cardiotoxic effects of delivering trastuzumab along with anthracyclines is an ongoing concern, rates of depressed left ventricular ejection fraction after 24 weeks of treatment were 7.1% in the sequential treatment arm and 4.6% in the concurrent treatment group.

“However,” Dr. Hunt and colleagues point out, “because of the small sample size, differences between treatments in terms of cardiac tolerability during neoadjuvant treatment might not have been evident.”

Overall, they conclude, “Concurrent administration of trastuzumab with anthracyclines offers no additional benefit and is not warranted.”

The authors of an accompanying editorial agree with that assessment, “although not because of lack of safety nor lack of efficacy.”

Drs. Shannon Puhalla, and Adam Brufsky at the University of Pittsburgh Cancer Institute, Pennsylvania, explain that that dual HER2 blockade has now entered neoadjuvant treatment for early breast cancer.  “The substantial benefit of combined HER2-targeted neoadjuvant treatment probably renders the question of anthracycline with concurrent trastuzumab versus sequential trastuzumab irrelevant.”

SOURCE: Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial

SOURCE:  Treatment of HER2-positive breast cancer: looking backwards briefly

Lancet Oncol 2013.