NEW YORK (Reuters Health) - Substituting nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for solvent-based paclitaxel when treating metastatic breast cancer increases the proportion of patients achieving pathological complete response after anthracycline-based chemotherapy, according to researchers in Germany.
The researchers conducted a phase 3 randomized trial in which patients were treated with nab-paclitaxel or solvent-based paclitaxel, followed by intravenous epirubicin plus intravenous cyclophosphamide (EC), according to an article online February 8 in The Lancet Oncology.
"Nab-paclitaxel followed by standard EC is increasing the pathological complete response rate compared to paclitaxel followed by EC," Dr. Sibylle Loibl, of the German Breast Group in Berlin, told Reuters Health by email. "This is especially important for patients with a triple-negative tumor. The pathological complete response rate could almost be doubled in this group."
The study involved 1,206 women, 606 assigned to nab-paclitaxel and 600 assigned to solvent-based paclitaxel. Patients received 12 weeks of treatment.
The nab-paclitaxel group received 150 mg/m2 intravenously at first, then after a protocol amendment, 125 mg/m2 on days 1, 8, and 15 for four three-week cycles. The solvent-based paclitaxel group received 80 mg/m2 intravenously at the same times. Both groups also received EC treatment on day 1 of four three-week cycles. HER2-positive patients received trastuzumab and pertuzumab treatments on day 1 of each cycle.
Pathological complete response occurred in 233 (38.4%) of the nab-paclitaxel patients, compared to 174 (29%) of the solvent-based paclitaxel patients (odds ratio, 1.53; unadjusted p=0.00065). Patients with triple-negative breast cancer (n=276, 23%) experienced a "pronounced effect" (OR, 2.61; p=0.00020) with nab-paclitaxel.
Grade 3-4 anemia occurred in 13 (2%) of nab-paclitaxel patients, compared to four (1%) in the solvent-based paclitaxel patients, while grade 3-4 peripheral sensory neuropathy occurred in 63 (10%) of nab-paclitaxel patients taking any dose, in 31 (8%) of patients receiving the smaller dose and in 32 (15%) of patients taking the larger dose. That compares to 16 patients (3%) on solvent-based paclitaxel (p<0 .001="" p="">
Overall, 283 patients (23%) had at least one serious adverse event, 156 (26%) in the nab-paclitaxel group versus 127 (21%). Three deaths occurred in the nab-paclitaxel group due to sepsis, diarrhea, and unrelated accident, compared to one death (due to cardiac failure) in patients receiving solvent-based paclitaxel.
"The dose of nab-paclitaxel was reduced from initially 150mg/m2 to 125mg/m2 in the trial due to toxicity," Dr. Loibl told Reuters Health. "Peripheral sensory neuropathy is still higher than with paclitaxel, which was known before. But we need more data and we are currently following all women with a neuropathy" in order to develop a risk-benefit profile.
"The main question is, 'does this improvement in pathological complete response translate into a longer disease-free and eventually overall survival?' We need to collect long-term outcome and follow-up data. It would also be good to have a confirmatory trial," she said.
In an accompanying editorial comment, Dr. Marco Colleoni, of the European Institute of Oncology and International Breast Cancer Study Group in Milan, Italy, writes, "The results of the present study are important and helpful for the design of new treatment strategies including nab-paclitaxel, especially for tailored investigations in selected subtypes, such as triple negative disease. Meanwhile, results from ongoing studies with a similar design (eg, the ETNA trial NCT01822314), as well as survival data, are required before any modification of current clinical practice can be made."
Celgene and Roche supported this research. Several authors reported financial ties to the companies.
SOURCE: http://bit.ly/1VnlVMI and http://bit.ly/1U7WaBJ
Lancet Oncol 2016.
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