Abstract P1-16-05: Oraxol + Encequidar (OPac+E) vs IV paclitaxel (IVPac) in the treatment of patients with metastatic breast cancer (mBC) (Study KX-ORAX-001): Subgroup survival analysis of patients with hepatic dysfunction
Authors: Umanzor Gerardo , Rugo Hope S , Barrios Francisco J , Vasallo R H , Chivalan Marco A , Bejarano S , Ramirez Julio Roberto , Fein Luis , Kowalyszyn R D , Cutler D L , Kramer D , Wang H , Kwan R MF 
Published: March 2022

Abstract
Background: IVPac is widely used to treat patients with breast cancer. oPac+E is oral paclitaxel in combination with Encequidar, an oral, minimally absorbed, specific p-glycoprotein inhibitor that enables the absorption of oral paclitaxel. Results of the phase III trial, KX-ORAX-001, were presented at SABCS, 2019, Abstract # GS6-01. At the time of the database lock for the final analysis of the primary endpoint of confirmed tumor response rate, analyses of PFS and OS were performed. The confirmed tumor response rate was significantly higher in the oPac+E group vs IVPac (35.8% vs 23.4%, p=0.011 ITT, population). The median overall survival, as of Sept 2020 presented at SABCS 2020, Abstract# PD1-08 was 22.7 months vs 16.5 months, respectively favoring oPac. Analysis of safety data demonstrated that patients with elevated liver tests (at screening or baseline), were at increased risk of serious and early complications of neutropenia including sepsis, septic shock, febrile neutropenia which could be fatal. A post hoc, subgroup analysis of survival for patients with elevated liver tests was conducted. 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 received 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 randomized (oPac+E 265: IVPac 137) and represent the ITT population of which 399 subjects were dosed. 122 patients (oPac+E 74, IVPac 48) had elevated AST, or bilirubin (NCI ODWG mild category) at screening or predose/baseline. The subjects were generally balanced between treatment groups for mean age (55 vs 57 years), extent of tumor metastases, and tumor markers ER/PR+ HER2- (62% vs 63%), ER/PR- HER2- (11% vs 15%). For subjects receiving OPac+E, the median survival was 18.9 months vs 10.1 months for subjects receiving IVPac; with a hazard ratio of 0.593 (95.5% CI 0.382 - 0.921) favoring OPac+E.Greater than 65% of subjects had a survival event at the time of this analysis. Conclusion: Although patients with mBC and mild hepatic dysfunction at baseline are at increased risk of early serious neutropenic and infectious/septic complications after treatment with oPAC+E, this risk is counterbalanced by an increase in overall survival. (NCT 02594371)
Citation Format: Gerardo Umanzor, Hope S Rugo, Francisco J Barrios, R H Vasallo, Marco A Chivalan, S Bejarano, Julio Roberto Ramirez, Luis Fein, R D Kowalyszyn, D L Cutler, D Kramer, H Wang, R MF Kwan. Oraxol + Encequidar (OPac+E) vs IV paclitaxel (IVPac) in the treatment of patients with metastatic breast cancer (mBC) (Study KX-ORAX-001): Subgroup survival analysis of patients with hepatic dysfunction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-05.