Short Course of Chemo Effective in Early-Stage HER2 Breast Cancer

Combining four cycles of docetaxel and cyclophosphamide with 1 year of trastuzumab may be a viable treatment option for women with HER2-amplified early-stage breast cancer regardless of their TOP2A status, according to the results of a phase II study published in the Lancet Oncology.

“The short course of docetaxel/cyclophosphamide plus [trastuzumab] was an effective treatment for our population and offers women a shorter course of chemotherapy with [trastuzumab],” said study researcher Stephen E. Jones, MD, of US Oncology Research, McKesson Specialty Health, The Woodlands, Texas.

Previous research had shown that four cycles of docetaxel/cyclophosphamide had superior disease-free survival and overall survival compared with doxorubicin/cyclophosphamide. Specifically, docetaxel/cyclophosphamide was thought to be more effective in patients with HER2-amplified breast cancer.

To explore the addition of trastuzumab to this non-anthracycline regimen, Dr. Jones and colleagues enrolled 493 patients aged 18 to 75 years for treatment with four 21-day cycles of intravenous docetaxel plus cyclophosphamide plus trastuzumab.

All patients had an ECOG performance status of 1 or less, HER2-amplified disease, and adequate tumor specimen for analysis. The study also included women typically excluded from clinical trials with cancers less than 1 cm and negative nodes, according to Dr. Jones. The patients were followed for a median of 36.1 months.

At follow-up, the 190 women with TOP2A-amplified disease had a 2-year disease-free survival of 97.8% and 2-year overall survival of 99.5%. The 248 women with TOP2A-non-amplified disease had a 2-year disease-free survival of 97.9% and a 2-year overall survival was 98.8%.

Women with cancers less than 1 cm with negative nodes had 100% disease-free survival and overall survival at 3 years, suggesting that “maybe these patients could be treated with trastuzumab alone in a trial setting,” Dr. Jones said.

The most commonly reported adverse events reported by patients who received at least one dose of trastuzumab were fatigue (58.4%), neutropenia (51.4%), and nausea (44.7%). Cardiac dysfunction occurred in 6% of patients.

In an editorial that accompanied the article, Alessandra Gennari, MD, of EO Ospedali Galliera, Genova, Italy, and Lucia Del Mastro, MD, of the Istituto Nazionale per la Ricerca sul Cancra, Genova, Italy, questioned the researchers conclusion that “a short four-cycle regimen of docetaxel and cyclophosphamide combined with trastuzumab could be an option for adjuvant treatment of women with lower risk HER2-amplified early breast cancer.”

“A short-course of an anthracycline-free regimen, as investigated by Jones and colleagues, is a very attractive option; however, the harms of using a potentially less effective regimen, in view of its short duration, and the omission of an anthracycline, a toxic, but very active option in HER2-amplified disease, should be taken into account,” they wrote.

Based on having only 2-years of follow-up data, the editorialists wrote that the proposed regimen “cannot yet be deemed a viable option for patients with HER2-positive breast cancer, irrespective of their risk of recurrence.”