Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2018 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Safety and efficacy of eflapegrastim in reducing severe neutropenia in patients treated with myelosuppressive chemotherapy in a phase 3 randomized controlled trial compared to pegfilgrastim (ADVANCE trial).
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr e12513)
Author(s): Lee Steven Schwartzberg, Zandong Yang, Julio Antonio Peguero, Richy Agajanian, Jayaram S. Bharadwaj, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Gajanan Bhat, Patrick Wayne Cobb; University of Tennessee Health Sciences Center, Memphis, TN; Inovio Pharmaceuticals, Plymouth Meeting, PA; Oncology Consultants PA, Department of Research, Houston, TX; The Oncology Institute of Hope and Innovation, Downey, CA; Pacific Cancer Medical Center, Anaheim, CA; Texas Onc PA, McAllen, TX; Bond Clinic PA, Winter Haven, FL; WVU Cancer Institute of WVU Medicine, Morgantown, WV; Spectrum Pharmaceuticals, Irvine, CA; Frontier Cancer Center, Billings, MT
Background: Eflapegrastim is a novel investigational biologic comprised of recombinant human G-CSF covalently linked to the human immunoglobulin G4FC fragment using proprietary LAPSCOVERY™ technology with potentially unique distribution to areas rich in FcRn receptors. The current study was a randomized, phase 3 study to demonstrate the non-inferiority (NI) of eflapegrastim to pegfilgrastim in patients receiving chemotherapy for breast cancer. Methods: Patients with Stage I to Stage IIIA breast cancer were treated on Day 1 of each of four cycles with adjuvant/neo-adjuvant docetaxel and cyclophosphamide (TC). On Day 2 of each cycle patients received a single subcutaneous dose of either eflapegrastim 13.2 mg/0.6 mL (equivalent to 3.6 mg G-CSF) or pegfilgrastim (6 mg) in a 1:1 ratio. Patients had CBCs drawn daily on Day 1 and day 4-15 or until recovery of neutropenia in each cycle. The primary endpoint was to demonstrate non-inferiority of eflapegrastim to pegfilgrastim as measured by the mean duration of severe neutropenia (DSN) in Cycle 1 with NI margin of < 0.62 day. Results: In a total of 406 intent-to-treat patients (randomized to 196 eflapegrastim; 210 pegfilgrastim), median age was 61 years (range 24 to 84 years); mean (SD) DSN was 0.19 (0.478) days for eflapegrastim and 0.34 (0.668) days for pegfilgrastim, demonstrating the non-inferiority (95% CI of ∆DSN: [-0.260, -0.035]; p < 0.0001). The non-inferiority of eflapegrastim for DSN was maintained across all 4 cycles. There were no statistically significant differences in secondary endpoints of time to ANC recovery, depth of ANC nadir and incidence of FN at Cycle 1. The adverse events observed in ≥10% of patients were similar across both arms and were mainly hematologic including neutropenia, lymphopenia, anemia and leukopenia. Conclusions: Eflapegrastim, a novel long acting G-CSF was non-inferior to pegfilgrastim in the reduction of DSN in Cycles 1-4, in breast cancer patients treated with TC. Eflapegrastim was safe and well-tolerated with a similar safety profile to pegfilgrastim. Clinical trial information: NCT02643420
1. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score.