Patients who took nanoparticle albumin-bound (NAB)-paclitaxel had significantly better invasive disease-free survival (iDFS) compared with those who took solvent-based (sb)-paclitaxel as neoadjuvant therapy for primary breast cancer.
Previously, NAB-paclitaxel was found to be more effective than sb-paclitaxel in metastatic breast cancer, and earlier results showed an improved pathologic complete response rate (pCR) in the early breast cancer setting.
“Although in general individual patients with a pCR (pathologic complete rate) also have an improved disease-free survival and overall survival, on a study level a pCR increase does not always translate into a significantly better long-term outcome,” wrote study authors led by Michael Untch, MD, PhD, of Helios Klinikum Berlin-Buck in Germany. They reported the longer term iDFS outcome from the GeparSepto trial, first published online in May in the Journal of Clinical Oncology.
The study included a total of 1,206 patients, randomized to receive either 12-times weekly NAB-paclitaxel (606 patients) or sb-paclitaxel (600 patients) in the neoadjuvant setting. Patients then received epirubicin plus cyclophosphamide, and those with HER2-positive disease also received trastuzumab and pertuzumab concurrently with chemotherapy. They were followed for a median of 49.6 months.
During the follow-up period, there were a total of 243 iDFS events, including 143 in the sb-paclitaxel group and 100 in the NAB-paclitaxel patients. The iDFS rate at four years was 84.0% with NAB-paclitaxel, compared with 76.3% with sb-paclitaxel, for a hazard ratio of 0.66 (95% CI, 0.51–0.86; P = 0.002). However, there was no significant difference with regard to overall survival, at 89.7% and 87.2%, respectively, for an HR of 0.82 (95% CI, 0.59–1.16; P = 0.260). Results were similar across subgroups.
Patients who achieved a pCR were less likely to experience an iDFS event, at 8.9% compared with 25.6% for those who did not achieve a pCR.
A total of 355 patients (29.4%) reported grade 2–4 peripheral sensory neuropathy (PSN); 6.6% had grade 3–4 neuropathy during treatment. The median time to resolve grade 2–4 PSN to grade 1 was shorter in patients who received a NAB-paclitaxel dose of 125 mg/m2 compared to those who received 150 mg/m2; there was no difference between sb-paclitaxel and the 125 mg/m2 NAB-paclitaxel dose.
“The long-term results support the use of NAB-paclitaxel 125 mg/m2 instead of sb-paclitaxel in patients with early BC,” the authors concluded.
In an editorial, Masey Ross, MD, MS, and Charles E. Geyer Jr., MD, of Virginia Commonwealth University School of Medicine in Richmond, noted the “strikingly consistent” results across triple-negative and HR-positive/HER2-negative subgroups. They wrote, though, that other trials have yet to demonstrate improvements in event-free survival or other outcomes with NAB-paclitaxel.
“Nonetheless, the robust and clinically meaningful improvements in iDFS demonstrated with the dose and schedule employed in the GeparSepto trial, may still justify consideration of substitution of nab-paclitaxel for s-paclitaxel in neoadjuvant therapy for patients with higher-risk HER2-negative breast cancers,” they wrote.