1084 -oral paclitaxel in the treatment of metastatic ......1084 -oral paclitaxel in the treatment of...

1084 - Oral paclitaxel in the treatment of metastatic breast cancer (MBC) patientsDai MS1, Chao TY2, Chao TC3, Chiu CF4, Lu YS5, Shiah HS6, YY Wu1, WH Cheng2, Hung N7, Fetterly G7,

Cutler DL7, Kwan R7, Kramer D7, Chan W7, Hung T81Division of Hematology/Oncology, Tri-Service General Hospital, Taipei, Taiwan., 2Division of Hematology-Oncology, Taipei Medical University- Shuang Ho Hospital, New Taipei City, Taiwan . 3Division of Medical Oncology,

Taipei Veterans General Hospital, Beitou District, Taipei, Taiwan, 4Department of Medical Oncology, China Medical University Hospital, Taichung, Taiwan, 5Department of Medical Oncology, National Taiwan University Hospital, Taipei, Taiwan, 4Department of Medical Oncology, China Medical University Hospital, Taichung, Taiwan, 5Department of Medical Oncology, National Taiwan University Hospital, Taipei, Taiwan 7University of Otago,

Dunedin, New Zealand 7Athenex, Buffalo, NY, 8Zenith Technology Corporation Limited, Dunedin, New Zealand.

ClinicalTrials.gov Identifier: NCT03165955

INTRODUCTION

Intravenous (IV) paclitaxel is an effective treatmentfor breast cancer. Oral administration paclitaxel ispreferable to IV regarding minimizing IV injections,anaphylactic reactions to cremaphor, steroid pre-medications, hospital visits, and relevant costs.However, paclitaxel has poor oral absorption dueto active excretion by P-glycoprotein (Pgp) in theintestinal cells. Oraxol (Athenex, USA) is an oralpaclitaxel and HM30181, a novel oral inhibitor ofintestinal P-gp which enables the oraladministration of paclitaxel. We report the finalresults of a pharmacokinetics (PK) study, includingclinical response and tolerability of Oraxol intreatment of metastatic breast cancer patients.

Multicenter, single-arm, open-label, PK study of Oraxol(HM30181A at 15mg, plus oral paclitaxel 205mg/m2)administered orally for 3 consecutive days weekly for up to16 weeks. Paclitaxel PK was assessed at week-1 and week-4. Tumor Response was measured at weeks 8 and 16 usingRECIST criteria 1.1. Toxicity was assessed using CTCAEv4.03.

RESULTS

MATERIALS AND METHODS

Twenty-eight MBC patient were studied with a mean age of56.6 years (range: 38 - 79 yrs). 26 patients had failedmutiple previous chemotherapies. There were 11 (42.3%)partial response, 12 (46.2%) stable disease and 3 (11.5%)progressive disease in 26 evaluable patients. Threepatients had treatment-related SAEs (grade ≥3 neutropenia)and all patients recovered completely. PK results showedthat the AUC of oral paclitaxel at week-1 was reproducibleat week-4 (3050 to 3594 ng-hr/mL).

CONCLUSION1. Weekly oral paclitaxel can achieve paclitaxel exposure

similar to that of weekly IV paclitaxel (80mg/m2) reportedpreviously. PK of oral paclitaxel is reproducible.

2. Oraxol appears effective in the treatment of advanced breastcancer patients. The tumor response rate (PR= 42.3%, SD=46.2%) of Oraxol in treatment of metastatic breast cancerpatients who failed previous chemotherapies is veryencouraging.

3. The drug toxicity profile of Oraxol appears tolerable

HM30181: MOA