Randomized, multi-centric, open-label comparative study to evaluate efficacy and safety of biosimilar pegfilgrastim and reference pegfilgastrim in patients with chemotherapy induced neutropenia (cin)

Background: Pegfilgrastim is the most widely used long-acting G-CSF available worldwide in the management of febrile neutropenia during chemotherapy. Objective: The present multicentre study evaluated efficacy and safety of pegfilgrastim biosimilar against innovator reference pegfilgrastim, when given subcutaneously in patients with Chemotherapy Induced Neutropenia (CIN). Methods: A prospective, multi-centre, randomized, double-blind, two-arm, parallel group, active-control, comparative clinical study to evaluate efficacy and safety of biosimilar pegfilgrastim (study arm)/ innovator pegfilgrastim (reference arm) in patients with Chemotherapy Induced Neutropenia. A total of 105 patients were enrolled in in two arms i.e. study pegfilgrastim and innovator pegfilgrastim. The primary objective of the study was to evaluate the duration of Grade 4 neutropenia in patients receiving study drug / reference drug in the 1st cycle of chemotherapy during the study and the secondary objectives of the study were to study the incidence of Grade 4 neutropenia, the incidence and duration of febrile neutropenia, time to ANC recovery after ANC nadir and the depth of ANC nadir in Cycles 1 to 4. Results: Mean duration of Grade 4 neutropenia was 1.43 days in the study arm and 2.00 days in the reference arm. In the secondary efficacy analysis, most cases of Grade 4 neutropenia occurred in the first cycle. No cases of Grade 4 neutropenia were noted during cycle 2 in either of the treatment arms. The incidence of Grade 4 neutropenia in the study arm was 4.76% in cycle 3 and 1.11% in cycle 4. The incidence of Grade 4 neutropenia in the reference arm was 6.25% in cycle 3. There was no statistically significantly difference between the study and reference arm during cycle 3.(P= 0.759). No subject in either arm developed febrile neutropenia in any of the cycles other than this sporadic case. The depth of ANC nadir in study arm was lowest in cycle 1, (2.914 x109/L) and in reference arm, the depth of ANC nadir was lowest in cycle 4 (3.23 x109/L). The mean time to ANC recovery (≥2.0x109/L) after the ANC nadir in study arm and in reference arm was comparable. Observed difference between two arms in 2nd, 3rd, and 4th cycle was statistically insignificant. Conclusion: The biosimilar pegfilgrastim was found to be as effective and safe as reference pegfilgrastim product. The analysis of secondary endpoints were consistent with those of the primary endpoint, with reduction in incidence and duration of grade 4 neutropenia and febrile neutropenia.