Abstract P2-15-04: Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study)
Authors: Kato Hiroaki , Hara Fumikata , Kitada Masahiro , Takahashi Masato , Kikawa Yuichiro Kikawa Yuichiro , Sakata Eiko , Naito Yoichi , Hasegawa Yoshie , Saito Tsuyoshi , Iwasa Tsutomu , Tsurutani Junji , Taira Naruto , Takashima Tsutomu , Kashiwabara Kosuke , Aihara Tomohiko Aihara Tomohiko , Mukai Hirofumi 
Published: March 2020

Abstract
OBJECTIVE: Nab-paclitaxel (nab-PTX) has superior efficacy compared to conventional paclitaxel in metastatic breast cancer (MBC), but chemotherapy-induced peripheral neuropathy (CIPN) is more frequent with nab-PTX. In a single arm phase 2 trial (CA002-0LD), low dose nab-PTX (175 mg/m2) every 3 weeks (q3w) resulted in a good objective response rate (39.5%) without CIPN of grade 3 or higher. Therefore, we conducted a randomized controlled study to evaluate the optimal dose of nab-PTX by comparing a low dose (LD) and a medium dose (MD) to the standard dose (SD). Here, we evaluate the patients-reported outcomes (PROs) and health-related quality of life (HRQoL) in the ABROAD study.
PATIENTS AND METHODS: Three different doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2) were administered in patients with HER2-negative metastatic breast cancer. The primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates with the three doses were estimated by logistic regression. The optimal dose was selected by 2-step selection. First, if the hazard ratio (HR) for PFS was &lt;0.75 or &gt;1.33, the inferior dose was dropped. Then, a dose with an estimated incidence of grade 3/4 neurotoxicity &gt;10% was also dropped. PROs and HRQoL were assessed as secondary endpoints at baseline, and during the 2nd, 4th and 6th courses of protocol treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Patient Neurotoxicity Questionnaire (PNQ), Cancer Fatigue Scale (CFS) and EuroQol 5 Dimension (EQ-5D). The primary outcome for PROs and HRQoL was the FACT-Taxane trial outcome index (TOI), and inter-group comparison was performed using a mixed effect model for repeated measures (MMRM). This trial was registered with the University Hospital Medical Information Network (UMIN), Japan (protocol ID C000012429).
RESULTS: A total of 141 patients were randomly assigned to SD (n=47), MD (n=46) or LD (n=48) nab-PTX. PFS analysis showed that LD nab-PTX at 180 mg/m2/3 weeks was the optimal dose with good clinical efficacy and tolerability for patients with MBC (reported by Hara at ASCO2019). Longitudinal analysis (MMRM) showed that the difference from the baseline FACT-Taxane TOI score at MD and LD were significantly better than that at SD (MD vs. SD p&lt;0.001, LD vs. SD p&lt;0.001). Differences from baseline for the FACT-Taxane total score, physical well-being sub-score, and emotional well-being sub-score at MD and LD were also better than at SD. The difference from baseline for the CFS score at LD was better than that at SD (p=0.013) and those for EQ-5D utility scores at MD and LD were better than that at SD (MD vs. SD p=0.011, LD vs. SD p&lt;0.001). There were no significant differences for the PNQ.
CONCLUSION: Our results show that low dose nab-PTX at 180 mg/m2/3 weeks could be an optimal dose for PFS and from the perspectives of PROs and HRQoL.
Citation Format: Hiroaki Kato, Fumikata Hara, Masahiro Kitada, Masato Takahashi, Yuichiro Kikawa Yuichiro Kikawa, Eiko Sakata, Yoichi Naito, Yoshie Hasegawa, Tsuyoshi Saito, Tsutomu Iwasa, Junji Tsurutani, Naruto Taira, Tsutomu Takashima, Kosuke Kashiwabara, Tomohiko Aihara Tomohiko Aihara, Hirofumi Mukai. Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-04.