This article is more than 5 years old. Information may no longer be current.
Taxane-first sequencing improved response in breast cancer
The sequence of taxane chemotherapy before anthracyclines improved the pathologic complete response of patients with breast cancer compared with the reverse sequence, according to phase 3 study results.
However, the addition of gemcitabine had no effect on response, according to researchers.
The study included 831 patients who received adjuvant therapy in one of four dosing schedules. The regimens included epirubicin and cyclophosphamide followed by paclitaxel (n=207); paclitaxel followed by epirubicin and cyclophosphamide (n=208); epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine (n=208); and paclitaxel and gemcitabine followed by epirubicin and cyclophosphamide (n=208).
Among the 828 evaluable patients, 25% had inflammatory or locally advanced disease, 33% had ER-negative disease and 27% had HER-2–positive disease. The tumor size was larger than 50 mm in 20% of patients, and 50% of patients had involved axillary nodes.
Median follow-up was 47 months (interquartile range, 37-51).
Seventeen percent (95% CI, 14-21) of patients who received epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine achieved a pathologic complete response, which was not statistically different from the 17% (95% CI, 14-21) of patients who received the same regimen without gemcitabine (P=.98).
More patients who received paclitaxel first, with or without gemcitabine, achieved a pathologic complete response (20%; 95% CI, 16-24) compared with patients who received epirubicin and cyclophosphamide first (15%; 95% CI, 11-18).
The most common grade 3 adverse events were neutropenia (21%), infection (8%), fatigue (5%), muscle and joint pain (5%), and nausea (5%). Eighty-six patients (11%) developed grade 4 neutropenia, and three patients (<1%) experienced grade 4 infection.
“Taxane-first sequences allow early treatment with concomitant trastuzumab (Herceptin, Genentech) and bevacizumab (Avastin, Genentech), which might provide additional therapeutic advantage, shown for trastuzumab in the FinHer study,” the researchers wrote. “Both the NSABP-B40 and ARTemis trials of bevacizumab have adopted taxane-first sequencing for this reason. Because all patients receive both taxane and anthracycline components, taxane-first sequencing could be considered in all similar block-sequential adjuvant and neoadjuvant protocols.”
Aron Goldhirsch
Further analyses are necessary to determine the influence of tumor biology on the benefits of the taxane-first sequencing, Marco Colleoni, MD, and Aron Goldhirsch, MD, both of the European Institute of Oncology, wrote in an accompanying editorial.
“We favor consideration of available information suggesting the biological heterogeneity of the disease,” Colleoni and Goldhirsch wrote. “Therefore, investigations of tailored neoadjuvant treatments should aim at specific groups of patients selected according to criteria of hypothetical responsiveness through international collaboration. This strategy will be key for progress to be made in the treatment of individual patients with locally advanced breast cancer.”
Disclosure: The researchers report honoraria and researching funding from Bristol-Myers Squibb and Eli Lilly. Colleoni and Goldhirsch report no relevant financial disclosures.