ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension)(二十)
e area basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1 to 5% of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration was observed in single-dose toxicology studies in rodents administered paclitaxel formulated as albumin-bound particles at doses lower than the recommended human dose; doses were 54 mg/m2 in rodents and 175 mg/m2 in dogs.
14 CLINICAL STUDIES
14.1 Metastatic Breast Cancer
Data from 106 patients accrued in two single arm open label studies and from 460 patients enrolled in a randomized comparative study were available to support the use of ABRAXANE in metastatic breast cancer.
Single Arm Open Label Studies
In one study, ABRAXANE was administered as a 30-minute infusion at a dose of 175 mg/m2 to 43 patients with metastatic breast cancer. The second trial utilized a dose of 300 mg/m2 as a 30-minute infusion in 63 patients with metastatic breast cancer. Cycles were administered at 3-week intervals. Objective responses were observed in both studies.
Randomized Comparative Study
This multicenter trial was conducted in 460 patients with metastatic breast cancer. Patients were randomized to receive ABRAXANE at a dose of 260 mg/m2 given as a 30-minute infusion, or paclitaxel injection at 175 mg/m2 given as a 3-hour infusion. Sixty-four percent of patients had impaired performance status (ECOG 1 or 2) at study entry; 79% had visceral metastases; and 76% had > 3 sites of metastases. Fourteen percent of the patients had not received prior chemotherapy; 27% had received chemotherapy in the adjuvant setting, 40% in the metastatic setting and 19% in both metastatic and adjuvant settings. Fifty-nine percent received study drug as second or greater than second-line therapy. Seventy-seven percent of the patients had been previously exposed to anthracyclines.
In this trial, patients in the ABRAXANE treatment arm had a statistically significantly higher reconciled target lesion response rate (the trial primary endpoint) of 21.5% (95% CI: 16.2% to 26.7%), compared to 11.1% (95% CI: 6.9% to 15.1%) for patients in the paclitaxel injection treatment arm. See Table 11. There was no statistically significant difference in overall survival between the two study arms.
Table 11: Efficacy Results from Randomized Metastatic Breast Cancer Trial a Reconciled Target Lesion Response Rate (TLRR) was the prospectively defined protocol specific endpoint, based on independent radiologic assessment of tumor responses reconciled with investigator responses (which also included clinical information) for the first 6 cycles of therapy. The reconciled TLRR was lower than the investigator Reported Response Rates, which are based on all cycles of therapy.
b From Cochran-Mantel-Haenszel test stratified by 1st line vs. > 1st line therapy.
c Prior therapy included an anthracycline unless clinically contraindicated.
ABRAXANE
260 mg/m2 Paclitaxel Injection
175 mg/m2
Reconciled Target Lesion Response Rate (primary endpoint)a
All randomized patients Response Rate
[95% CI] 50/233 (21.5%)
[16.19% – 26.73%] 25/227 (11.1%)
[6.94% – 15.09%]
p-valueb 0.003
Patients who had failed combinati |
