Cancer Res Treat.  2023 Jul;55(3):766-777. 10.4143/crt.2022.987.

Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies

• Moon YW
• Kim SK
• Lee KS
• Lee MH
• Park YH
• Park KH
• Kim GM
• Lim S
• Lee SA
• Choi JD
• Baek E
• Han H
• Baek S
• Im SA

• KMID: 2544160
• DOI: http://doi.org/10.4143/crt.2022.987

Abstract

Purpose
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
Materials and Methods
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
Results
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
Conclusion
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

Keyword

Breast neoplasms; Long-acting granulocyte-colony stimulating factor; Neutropenia; Koreans; Asians

Figure

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  Fig. 1 Study design diagram. G-CSF, granulocyte-colony stimulating factor; IV, intravenously; SC, subcutaneously.

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  Fig. 2 Patient disposition diagram (ADVANCE, RECOVER, and pooled data). The number of Asian patients includes Korean patients and non-Korean Asian patients. Total three patients (non-Asian; Eflapegrastim 1, Pegfilgrastim 2) was randomized, however, never received any study drug. One patient (non-Asian) was randomized to Pegfilgrastim but was given eflapegrastim on cycle 1 day 2. This patient was assigned to Eflapegrastim Safety population. ITT, intent-to-treat.

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  Fig. 3 Subgroup analyses of primary efficacy. a, primary analysis in intention-to-treat (ITT) population; b, sensitivity analysis in per protocol (PP) population. CI, confidence interval.

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  Fig. 4 Plot of mean (±standard error) absolute neutrophil count (ANC) over time by treatment in cycle 1. ANC values measured at day 1, day 4 through day 15, and day 22 were included. Day 1 ANC values of next cycle were depicted with values on day 22. SPI-2012 indicates eflapegrastim.

Reference

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