| Institution: | 1. Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan;2. Department of Breast Medical Oncology, Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan;3. Department of Breast Disease Center, Asahikawa Medical University Hospital, Asahikawa, Japan;4. NHO Hokkaido Cancer Center, Sapporo, Japan;5. Department of Breast Surgery, Kobe City Medical Center General Hospital, Kobe, Japan;6. Teine Keijinkai Hospital, Sapporo, Japan;7. Niigata City General Hospital, Niigata, Japan;8. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;9. Department of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, Japan;10. Japanese Red Cross Saitama Hospital, Saitama, Japan;11. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan;12. Okayama University Hospital, Okayama, Japan;13. Osaka City University Graduate School of Medicine, Osaka, Japan;14. Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan;15. Breast Center, Aihara Hospital, Minoh, Japan;p. National Cancer Center Hospital East, Kashiwa, Chiba, Japan |
| Abstract: | BackgroundChemotherapy-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.MethodsWe compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 SD260] vs Medium: 220 mg/m2 MD220] vs Low: 180 mg/m2 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.ResultsOne 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.ConclusionsIntravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC. |
