Shi, Y.K., Chen, Q., Zhu, Y.Z., He, X.H., Wang, H.Q., Jiang, Z.F., . . . Liu, X.Q. (2013). Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: A multicenter, randomized, crossover phase 3 study. Anti-Cancer Drugs, 24, 641–647.

To compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens

Fifteen centers enrolled 337 chemotherapy-naïve patients with cancer with normal bone marrow function. All patients were randomized into AOB and BOA arms and received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 mg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 lg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). In the AOB arm, 173 patients were enrolled and 155 completed the two cycles. In the BOA arm, 164 patients were enrolled and 142 completed the two cycles. Efficacy and safety parameters were recorded. The primary endpoint was the rate of protection against grade 4 neutropenia after chemotherapy (defined as the rate at which the absolute neutrophil count [ANC] remained greater than 0.5 x 10⁹/L throughout the entire cycle).

• N = 337  
• AGE = 18–70 years
• MALES: 68 (AOB), 60 (BOA); FEMALES: 101 (AOB), 97(BOA)
• KEY DISEASE CHARACTERISTICS: Primarily breast, non-small cell lung cancer, and non-Hodgkin lymphoma; study arms essentially equal, except the BOA arm did enroll two patients with head and neck cancer; stage of disease was split equally throughout both arms
• OTHER KEY SAMPLE CHARACTERISTICS: The groups were well matched with respect to demographics, history of disease, disease severity, and ANC at baseline. The median age of patients in the study was 50 years, and almost 40% of the patients were men. Breast cancer was the most common histology. About 50% of the enrolled patients previously had undergone surgery.

• SITE: Multi-site   
• SETTING TYPE: Outpatient   
• LOCATION: Republic of China

• SITE: Multi-site   
• SETTING TYPE: Outpatient   
• LOCATION: Republic of China

• Multi-center, randomized, open-label, crossover, noninferiority study

Blood samples were collected for complete blood counts with differential on days 0, 3, 5, 7, 9, 11, 13, 17, and 21 of each cycle. The primary efficacy endpoint was the rate of protection from grade 4 neutropenia (ANC remains greater than 0.5 through the entire cycle) after chemotherapy. The secondary efficacy endpoints included the rate of grade 3/4 neutropenia, time to neutrophil recovery (defined as the time from chemotherapy administration until the ANC increased to 2.0 [after the expected nadir]), incidence of febrile neutropenia (ANC less than 0.5 and axillary temperature higher than 38.1°C), incidence of antibiotic administration, and ANC profile.

Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. In cycle 1, the rates of protection were 89.7% (pegylated filgrastim) and 89.5% (filgrastim). In cycle 2, no episodes of grade 4 neutropenia occurred. In subgroup analysis according to chemotherapy regimens, the protective rates of pegylated filgrastim did not differ significantly from the protective rates of filgrastim.

This trial provides direct evidence that pegylated filgrastim is comparable to filgrastim in efficacy and safety when administered in support for commonly used, standard-dose, mild-to-moderate myelosuppressive chemotherapy regimens. In addition, the single injection per cycle may lead to increased patient satisfaction and compliance.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Other limitations/explanation: Not clear that the sample was at risk for neutropenia

Increased use of pegylated filgrastim across solid tumor types with mild-to-moderate myelosuppressive chemotherapy regimens. The lower frequency of visits may lead to increased emergency department visits for toxicities that normally would be caught at the daily injection visits. Education will be key in this patient population. For some patients, avoidance of daily injections may be important.