Abstract PS13-34: Differential efficacy of pegfilgrastim (Peg) in patients (pts) with breast cancer (BC) versus other cancer types for the prevention of docetaxel (Doc) chemotherapy-induced neutropenia (CIN)
Authors: Blayney Douglas W. , Ginn Greg , Huang Lan , Mohanlal Ramon 
Published: February 2021

Abstract
Introduction: Peg and other G-CSFs are widely used in BC patients receiving myelosuppressive chemotherapy. We previously reported that Peg’s mechanism of action (MoA) for CIN -prevention protects in week 2 of the cycle. BC pts receiving Doc/Doxorubicin/Cyclophosphamide (TAC) are unprotected in week 1. [Study BPI-2358-106 (NCT03102606) Blayney, St Gallen 2019]. In this study, the novel CIN agent Plinabulin (Plin), with a MoA different, yet complimentary to Peg CIN, prevented severe CIN in week 1 of the Cycle (C), and given in combination with Pegflgrastim, offered superior protection throughout the entire cycle. Other Study 106 results indicated that monotherapy Peg is a sub-optimal CIN prophylaxis strategy in TAC-treated BC pts. In Study BPI-2358-105 (NCT03102606) we evaluated Peg monotherapy as CIN preventive therapy in BC pts.
Methods: In Study 105, BC, lung (NSCLC) and prostate cancer (HRPC) pts with at least 1 risk factor as per NCCN guidelines, received Doc 75 mg/m2 with either Peg 6mg (n=53) or Plin 40 mg (n=52), and had frequent blood draws in C1 for Neutrophil count assessment. Grade (Gr) 4 Neutropenia (N) frequency in C1, Duration of Severe Neutropenia (DSN) in C1, and frequency of clinical sequelae of N (Hospitalizations, Infections, FN, antibiotic use, chemotherapy dose reductions) in C1 to C4 were calculated in BC (n=27) and NSCLC/HRPC (n=26) pts receiving Doc 75 mg/m2. There were 9 pts in the HRPC group in the Peg arm.
Results:No HRPC and 4% (1pt) NSCLC pts of peg-treated developed Gr 4 N, whereas 16% of Peg-treated BC pts developed Gr 4 N. Gr 4 N frequency over time in C1 was significantly higher in BC pts vs NSCLC/HRPC pts (p&lt;0.016; Cochran-Mantel-Haenszel test; see table below) with Peg. DSN in BC pts was &gt;5 times longer (p&lt;0.005; NBR test) in BC pts vs NSCLC/HRPC pts. DSN was 0.36 Day (D) (95% CI: 0.28; 0.49) in BC pts vs 0.076 Day (95% CI: 0.03; 0.12) in NSCLC/HRPC pts with Peg. Numerically more BC pts vs NSCLC/HRPC pts had clinical sequelae of N with Peg.
Conclusions: In BC pts treated with Peg monotherapy after Doc 75 mg/m2, Peg is significantly less effective for CIN prevention compared to NSCLC/HRPC pts. The sub-optimal efficacy of Peg was due to its protection occurring in week 2 of the Cycle, leaving a significant number of pts unprotected in week 1 of the Cycle. The demonstrated effectiveness of Plinabulin in week 1 of the Cycle in BC pts, when combined with Peg could offer superior CIN protection vs Peg alone in BC pts receiving Doc.
Gr4N %BaselineC1D1C1D2C1D6*C1D7C1D8C1D9C1D10C1D15BC0%0%0%16%12%4%4%4%0%NSCLC/ HRPC0%0%0%4%4%0%0%0%0%*On C1D6, Gr 4 frequency in the Plin arm was 0% in BC pts
Citation Format: Douglas W. Blayney, Greg Ginn, Lan Huang, Ramon Mohanlal. Differential efficacy of pegfilgrastim (Peg) in patients (pts) with breast cancer (BC) versus other cancer types for the prevention of docetaxel (Doc) chemotherapy-induced neutropenia (CIN) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-34.