A randomized phase II trial found that nab-paclitaxel showed equivalent efficacy and was well tolerated compared with docetaxel as neoadjuvant therapy in early-stage breast cancer.
A randomized phase II trial found that nab-paclitaxel showed equivalent efficacy and was well tolerated compared with docetaxel as neoadjuvant therapy in early-stage breast cancer.1
According to the authors, led by Takashi Kuwayama, MD, of Showa University School of Medicine, Tokyo, no significant differences were found in the pathologic complete response (pCR) rates among HER2-negative patients. The pCR rate was 17% in the nab-paclitaxel group and 12% in the docetaxel group.
“However, in the Ki67 high-expression group, weekly nab-paclitaxel showed a tendency toward a greater pCR compared with docetaxel,” they wrote inClinical Breast Cancer.In the Ki67 > 20% group, the pCR rate was 24% for the nab-paclitaxel arm and 16% for the docetaxel arm.
Additionally, the authors believe that nab-paclitaxel might be more effective in patients with highly proliferative cancer.
The trial endpoint was pCR, chosen due to its status as a possible prognostic factor for disease-free survival (DFS) and overall survival (OS). pCR was defined as no invasive tumor or noninvasive residual tumor in the breast or lymph nodes (ypT0 and ypN0). Secondary endpoints included the clinical response rate, histologic effect of treatment, breast conservation surgery rate, and toxicity.
The investigators enrolled a total of 152 eligible patients at 6 centers in Japan. All patients had histologically confirmed, invasive clinical stage T1c-T3cN0M0 or T1-T3N1M0 breast cancer and an ECOG performance status of 0 or 1. All patients were treatment-naive for the current breast cancer. Testing was carried out on all tumors to determine their estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status.
In the nab-paclitaxel group, the median age was 49. Of these patients, 61% had ER+ disease and 36% had triple-negative breast cancer (TNBC). Nearly two-thirds of patients (65%) in this group expressed Ki67 at 20% or more.
The median patient age in the docetaxel group was 51. Of these patients, 61% had ER+ disease, while 38% had TNBC. At 57%, the number of Ki67 >20% patients who received docetaxel was less than in the nab-paclitaxel group.
Patients were randomized to receive either 4 cycles of docetaxel (75 mg/m2on day 1) every 3 weeks or 4 cycles of nab-paclitaxel (100 mg/m2on days 1, 8, and 15) every 4 weeks. All patients then received 4 cycles of FEC (5-FU, 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) every 3 weeks.
The authors noted that the optimal dose of nab-paclitaxel has not yet been determined because “cumulative toxicity, including peripheral neuropathy, is seriously expressed after the administration of nab-paclitaxel. We divided treatment into weekly intervals for 3-week periods to improve the feasibility,” they wrote. “Therefore, we set the dose intensity of weekly nab-paclitaxel to be appropriate for a 3-week regimen (85 mg/m2/wk).”
Additionally, Kuwayama et al planned the current trial before the start of the GEPAR-SEPTO trial, which compared nab-paclitaxel and solvent-based paclitaxel for patients with early-stage breast cancer.2“Thus, the dose and schedule of nab-paclitaxel were different at 100 mg/m2on days 1, 8, and 15 every 28 days in the present study and 150 mg/m2weekly in the GEPAR-SEPTO trial,” they wrote.
Due to concerns regarding occurrences of serious peripheral neuropathy and rash, the nab-paclitaxel dose in the GEPAR-SEPTO protocol was reduced to 125 mg/m2from 150 mg/m2. However, in this study, no peripheral neuropathy higher than grade 3 occurred in the nab-paclitaxel group.
The most common grade 3/4 adverse event was neutropenia. In the nab-paclitaxel arm, 27 of 74 patients (36%) had grade 3 or 4 neutropenia, while 31 of 77 patients (40%) in the docetaxel arm did.
Peripheral sensory neuropathy of any grade was common, occurring in 49 patients (66%) in the nab-paclitaxel group and 42 patients (55%) in the docetaxel group. Other common nonhematologic adverse events of any grade were arthralgia, which affected 26 patients (35%) in the nab-paclitaxel group and 32 patients (42%) in the docetaxel group and myalgia, which affected about one-third of patients in each group.
Of the 109 patients (72%) for whom a clinical response was reported after 4 cycles of taxane, the response rate was slightly lower with docetaxel (44%) than with nab-paclitaxel (52%), the authors wrote. After completion of FEC, the corresponding clinical response rates were similar (53% and 57%).
The authors noted several study limitations. First, the assessment of tumor expression was done at the local level, not by a central review board. Second, it is not currently known whether a continuous or intermittent schedule of nab-paclitaxel is more effective in early breast cancer.
Finally, because patients in the nab-paclitaxel group underwent blood testing more frequently due to the dosing schedule, adverse events were more likely to be diagnosed in these patients.
Kuwayama et al plan to evaluate patient-reported outcomes in a future study.