Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

Abstract

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m 2 [SD260] vs Medium: 220 mg/m 2 [MD220] vs Low: 180 mg/m 2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m 2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.

Quality of life in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

“…Many of the QoL constituent domains showed a positive trend with low-dose nab-PTX, but SFWB showed the opposite trend, for unknown reasons. Primary endpoint analysis showed that intravenous administration of low-dose nab-PTX at 180 mg/m 2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity for patients with metastatic breast cancer [ 4 ]. The QoL substudy also showed that low-dose nab-PTX at 180 mg/m 2 q3w is optimal in terms of QoL and cancer-related fatigue.…”

“…Then, if the estimated incidence rate of grade 3/4 neuropathy was > 10%, the other dose was dropped. Primary analysis showed that low-dose nab-PTX at 180 mg/m 2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with metastatic breast cancer [ 4 ].…”

Quality of life in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

“…Primary endpoint analysis showed that intravenous administration of low-dose nab-PTX at 180 mg/m 2 q3w may be the optimal therapy with meaningful e cacy and favorable toxicity for patients with metastatic breast cancer [4]. The QoL substudy also showed that low-dose nab-PTX at 180 mg/m 2 q3w is optimal in terms of QoL and cancer-related fatigue.…”

“…Then, if the estimated incidence rate of grade 3/4 neuropathy was > 10%, the other dose was dropped. Primary analysis showed that lowdose nab-PTX at 180 mg/m 2 q3w may be the optimal therapy with meaningful e cacy and favorable toxicity in patients with metastatic breast cancer [4].…”

Albumin-Bound Paclitaxel: Worthy of Further Study in Sarcomas

“…Nab-paclitaxel improved the pathological complete response rate and event-free survival compared with traditional taxanes, and with acceptable toxicities (63). Current studies of nab-paclitaxel in breast cancer have focused on dose adjustment and combination regimens with other drugs (64)(65)(66)(67)(68). In conclusion, the application of nab-paclitaxel in breast cancer has gradually improved from second-line and above-to first-line and neoadjuvant therapy.…”