Metastatic breast cancer patients treated with an oral formulation of paclitaxel and encequidar showed better response, progression-free survival (PFS), and overall survival (OS), as well as less neuropathy compared with patients treated with intravenous paclitaxel. This method of administration may offer patients who do not live near clinics or hospitals a new perspective when this type of treatment is considered.
Paclitaxel is generally administered intravenously in the metastatic setting. In this trial, an oral form of the drug was evaluated , given in combination with encequidar, which is a highly specific p-glycoprotein pump inhibitor that allows oral paclitaxel to be absorbed into the bloodstream. Researchers enrolled 402 metastatic breast cancer patients who were randomly assigned in a 2:1 ratio to receive either 205 mg/m² of oral paclitaxel plus encequidar for 3 days a week (n=235), or 175 mg/m² paclitaxel intravenously every 3 weeks (n=125). Inclusion criteria consisted of histologically or cytologically confirmed breast cancer, measurable metastatic target lesion disease by RECIST v1.1 and ECOG performance status 0-1. Key exclusion criteria were central nervous system (CNS) metastasis and <1 year since previous taxane treatment (adjuvant or metastatic). Baseline patient characteristics and demographics were similar between the two treatment groups. The primary endpoint of the study was radiologically confirmed tumour response rate at 2 consecutive time points, whereas secondary endpoints were PFS and OS.
It was shown that 35.8% of patients treated with oral paclitaxel had a confirmed tumour response versus 23.4% of patients in the intravenous paclitaxel group. In evaluating the pre-specified modified intention-to-treat (ITT) population (excluding patients who did not have target tumours that could be evaluated by the central radiologist per RECIST or who did not receive sufficient treatments), the response rate in patients receiving oral paclitaxel was 40.4% versus 25.6% for patients in the intravenous paclitaxel group. When the durability of response was measured, researchers found that the response lasted more than 150 days in 51% of patients in the oral paclitaxel group with a confirmed response, compared with 38% of patients in the intravenous paclitaxel group. Ongoing analysis of PFS showed a median of 9.3 months for the oral paclitaxel group, compared with 8.3 months for the intravenous paclitaxel group. OS was 27.9 months for patients in the oral paclitaxel group versus 16.9 months for patients in the intravenous paclitaxel group.
Although higher rates of neutropenia, infection, and gastrointestinal adverse events (AEs) were observed in patients receiving oral paclitaxel, rates of neuropathy were lower in patients treated with oral paclitaxel than in patients receiving intravenous paclitaxel (17% vs 57%). Moreover, grade 3 neuropathic symptoms occurred in 1% of oral paclitaxel patients versus 8% of patients treated with intravenous paclitaxel. The risk of serious AEs on both treatments was highest among those patients who had pre-treatment evidence of hepatic impairment; the protocol was amended to address this issue. The next step will include testing the tolerability of oral paclitaxel in patients who are at high risk of developing peripheral neuropathy. The oral formulation may also be studied in other cancers, either as a monotherapy or in combination with other drugs.
- Cutler DL, et al. GS6-01. SABCS 2019.
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Table of Contents: SABCS 2019
Screening, Detection, and Diagnosis
Phase 2 Trial Update
Phase 3 Trial Update
Long-Term Study Results
Triple-Negative Breast Cancer
HER2-Positive Breast Cancer
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