ed doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 administered every 21 days for up to 4 cycles for the treatment of metastatic breast cancer. Study 1 investigated the utility of a fixed dose of Neulasta®. Study 2 employed a weight‑adjusted dose. In the absence of growth factor support, similar chemotherapy regimens have been reported to result in a 100% incidence of severe neutropenia (absolute neutrophil count [ANC]< 0.5 x 109/L) with a mean duration of 5‑7 days, and a 30%‑40% incidence of febrile neutropenia. Based on the correlation between the duration of severe neutropenia and the incidence of febrile neutropenia found in studies with Filgrastim, duration of severe neutropenia was chosen as the primary endpoint in both studies, and the efficacy of Neulasta® was demonstrated by establishing comparability to Filgrastim‑treated patients in the mean days of severe neutropenia.
In Study 1, 157 patients were randomized to receive a single subcutaneous injection of Neulasta® 6 mg on day 2 of each chemotherapy cycle or daily subcutaneous Filgrastim 5 mcg/kg/day beginning on day 2 of each chemotherapy cycle. In Study 2, 310 patients were randomized to receive a single subcutaneous injection of Neulasta® 100 mcg/kg on day 2 or daily subcutaneous Filgrastim 5 mcg/kg/day beginning on day 2 of each chemotherapy cycle.
Both studies met the primary objective of demonstrating that the mean days of severe neutropenia of Neulasta®-treated patients did not exceed that of Filgrastim‑treated patients by more than one day in cycle 1 of chemotherapy (see Table 1). The rates of febrile neutropenia in the two studies were comparable for Neulasta® and Filgrastim (in the range of 10% to 20%). Other secondary endpoints included days of severe neutropenia in cycles 2‑4, the depth of ANC nadir in cycles 1‑4, and the time to ANC recovery after nadir. In both studies, the results for the secondary endpoints were similar between the two treatment groups.
Table 1. Mean Days of Severe Neutropenia (in Cycle 1)
|
|
|
Study |
Mean days of severe neutropenia |
Difference in means
(95% CI) |
|
Neulasta®* |
Filgrastim
(5 mcg/kg/day)
|
|
Study 1
n= 157
|
1.8
|
1.6
|
0.2
(-0.2, 0.6)
|
|
Study 2
n= 310
|
1.7
|
1.6
|
0.1
(-0.2, 0.4)
|
Study 3 was a randomized, double-blind, placebo-controlled study that employed docetaxel 100 mg/m2 administered every 21 days for up to 4 cycles for the treatment of metastatic or non-metastatic breast cancer. In this study, 928 patients were randomized to receive a single subcutaneous injection of Neulasta® 6 mg or placebo on day 2 of each chemotherapy cycle. Study 3 met the primary objective of demonstrating that the incidence of febrile neutropenia (defined as temperature ≥ 38.2°C and ANC ≤ 0.5 x109/L) was lower for Neulasta®-treated patients as compared to placebo-treated patients (1% versus 17%, p < 0.0 |
