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Docetaxel-cyclophosphamide plus trastuzumab effective in HER-2–amplified early breast cancer
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Four cycles of docetaxel and cyclophosphamide, plus 1 year of trastuzumab, could be an effective adjuvant treatment regimen for women with lower-risk HER-2–amplified early breast cancer, according to results of an open-label, phase 2 study.
The regimen conferred benefits regardless of patients’ TOP2A status, researchers said.
Prior studies suggest docetaxel plus cyclophosphamide was associated with improved DFS and OS in women with HER-2–amplified early breast cancer when compared with doxorubicin plus cyclophosphamide.
In the current study, researchers set out to assess the use of docetaxel and cyclophosphamide, plus 1 year of trastuzumab (Herceptin, Genentech), in 493 patients.
The investigators also evaluated whether the treatment regimen was as effective in women with TOP2A-amplified and nonamplified disease.
All patients were aged 18 to 75 years; had Eastern Cooperative Oncology Group performance status of 1 or less; had operable, histologically confirmed, invasive carcinoma of the breast; demonstrated adequate hematological, renal, hepatic and cardiac function; and had adequate tumor specimen available for FISH analysis of TOP2A status.
Median follow-up was 36.1 months.
Researchers obtained TOP2A status for 438 of the patients.
Among the 190 patients with TOP2A-amplified disease, 2-year DFS was 97.8% (95% CI, 94.2-99.2) and 2-year OS was 99.5% (95% CI, 96.2–99.9). Among the 248 patients with TOP2A nonamplified disease, 2-year DFS was 97·9% (95% CI, 94.9–99.1) and 2-year OS was 98.8% (95% CI, 96.2–99.6).
The most common grade 3 and grade 4 adverse events were neutropenia (47.1%), fatigue (4.3%) and diarrhea (3.3%). In addition, cardiac dysfunction occurred in 6% of patients.
“Our data are promising up to 3 years of follow-up, with results being consistent with those obtained using much longer-duration chemotherapy regimens as reported in the major randomized trials,” the researchers wrote. “Additionally, we included 95 patients with node-negative cancers and tumors 1 cm or smaller in size and showed a 100% DFS at 3 years. Prospective data for such patients were, to the best of our knowledge, not available previously. Thus, a short regimen of four cycles of docetaxel and cyclophosphamide combined with 1 year of trastuzumab could be an option for many women with lower-risk HER-2–amplified early-stage breast cancer, irrespective of TOP2A status.”
Disclosure: The researchers report speakers’ bureau roles with Sanofi and Genentech, as well as consultant roles with Sanofi.
Perspective
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Adam M. Brufsky, MD, PhD, FACP
We are always trying to reduce the toxicity of adjuvant therapy for breast cancer, especially in situations where the efficacy of multiple regimens is excellent. One such situation is in the adjuvant therapy of HER-2–positive breast cancer, in which 5-year DFS approaches 85% to 90% with most of the common regimens. Recently, less cardiotoxic regimens such as TCH (docetaxel, carboplatin and trastuzumab) have been popularized over regimens containing AC (doxorubicin plus cyclophosphamide) and taxane/trastuzumab for this reason.
The article by Jones and colleagues is another step in this direction. For patients with lower-risk HER-2–positive breast cancer, a regimen of docetaxel/cytoxan for four cycles with trastuzumab concurrently for four cycles and then alone for 13 cycles was found to have an excellent toxicity profile and a 3-year DFS of more than 95%. Although this is a phase 2, nonrandomized trial, these results are very encouraging for those of us who wish to reduce the toxicity and length of adjuvant therapy for HER-2–positive, early-stage breast cancer while maintaining excellent efficacy.
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