Abstract PS13-06: Lower rates of neuropathy with oral paclitaxel and encequidar (oPac+E) compared to IV paclitaxel (IVPac) in treatment of metastatic breast cancer (mBC): Study KX-ORAX-001
Authors: Rugo H S , Umanzor G , Barrios F J , Vasallo R H , Chivalan M A , Bejarano S , Ramirez J R , Fein L , Kowalyszyn R D , Cutler D L , Kramer D , Goldfinch J , Wang H , Moore T , Kwan R MF 
Published: February 2021

Abstract
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity associated with IVPac. Primarily sensory, CIPN is an often irreversible condition primarily affecting the hands and feet associated with pain, numbness, tingling, and sensitivity to cold and has a significant impact on quality of life and treatment tolerance. Risk of CIPN increases with age, dose intensity, cumulative dose, and preexisting conditions including diabetes.
Methods: Study KX-ORAX-001 was a phase III, randomized, international study in women with mBC for whom treatment with IVPac was recommended. Eligible patients were randomized 2:1 to receive oPac+E or IVPac. Patients continued treatment until discontinuation due to progressive disease or toxicity. oPac 205 mg/m2 was given once daily for 3 days weekly. E 12.9 mg was given 1 hour before each dose of oPac. IVPac 175 mg/m2 was infused over 3 hours every 3 weeks. The primary endpoint was efficacy defined as tumor response confirmed by BICR at two consecutive evaluations. Key secondary endpoints included PFS, OS. Safety was monitored throughout the study.
Results: A total of 402 mBC patients were enrolled, 265 randomized to oPac+E and 137 to IVPac (ITT population). 399 patients were treated and comprise the safety population. The confirmed response rate was significantly greater in the oPac+E group vs IVPac (35% vs 23%) for the ITT population. Median overall survival was (27.7 vs 16.7 months, ITT) at the time of the analysis. Long-term follow up for final determination of PFS and OS is ongoing.Incidence of neuropathy-related TEAEs were lower in patients receiving oPac+E vs IVPac: Overall (21% vs 64%; all grades), grade ≥3 (2% vs 15%). Cumulative risk for neuropathy with IVPac was &gt;50% by week 8 and was 83% at week 88. In contrast, the cumulative risk of neuropathy with oPac+E rose slowly and plateaued at 34% at week 88. Treatment discontinuations due to neuropathy occurred only in the IVPac arm (8%). Dose reductions due to neuropathy were reported in 8% of IVPac treated patients and in 2% of oPac+E treated patients. In agreement with the lower rates of peripheral neuropathy in patients treated with oPac+E, there was lower use of medications used for the treatment of neuropathic symptoms. Use of gabapentin or pregabalin was 12% for patients receiving oPac+E vs 40% for IVPac treated patients.
Conclusions: oPac+E was associated with greater efficacy in the treatment of patients with mBC and a lower incidence of neuropathy, slower onset and lesser severity of neuropathic events compared to IVPac 175mg/m2 administered every three weeks. Fewer patients receiving oPac+E required dose reduction due to neuropathy and no patients receiving oPac+E discontinued treatment due to neuropathy. Reduction in neuropathy may improve quality of life and allow longer administration of effective therapy while maintaining dose intensity.
Citation Format: H S Rugo, G Umanzor, F J Barrios, R H Vasallo, M A Chivalan, S Bejarano, J R Ramirez, L Fein, R D Kowalyszyn, D L Cutler, D Kramer, J Goldfinch, H Wang, T Moore, R MF Kwan. Lower rates of neuropathy with oral paclitaxel and encequidar (oPac+E) compared to IV paclitaxel (IVPac) in treatment of metastatic breast cancer (mBC): Study KX-ORAX-001 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-06.