Abstract PS11-15: Plinabulin and pegfilgrastim (Plin+Peg) versus peg monotherapy (Peg) after TAC: A comparison of efficacy, safety, relative dose intensity (RDI) and bone pain
Authors: Blayney Douglas W. , Ginn Greg , Huang Lan , Mohanlal Ramon W. 
Published: February 2021

Abstract
Introduction:Prevention of Chemotherapy Induced Neutropenia (CIN) through primary or secondary prophylaxis is indicated in breast cancer (BC) chemotherapy (chemo) which is administered with curative intent. Granulocyte colony stimulating factors (G-CSFs), including Peg are standard of care in this context. In typical every three-week chemo regimens with primary G-CSF prophylaxis, absolute neutrophil count (ANC) nadir occur approximately day (D) 7, which reduces but does not eliminate febrile neutropenia risk in the first week. However, plinabulin (Plin), a novel non-G-CSF agent, protects against the nadir and CIN in the 1st week after chemo (Blayney ASCO 2019). These findings provided the rationale to combine Plin with Peg after chemo with a high febrile neutropenia risk. Both Plin and Peg act on the neutrophil precursor. Both agents mobilize bone marrow-derived CD34+ progenitor stem cells (Blayney ASH 2018). Plin has also anti-cancer efficacy in an animal BC model (Bertelsen, Int J Rad Biol 2011). Here we summarize the efficacy and safety data with combining Peg with Plin in potentially curable BC patients treated with TAC.
Methods: In the randomized phase 2 portion of Study 106 (NCT0329457), BC patients were treated with TAC (docetaxel 75, doxorubicin 50 and cyclophosphamide 500 mg/m2) and either 6 mg Peg alone (Peg6; n=22), or Peg 6mg+Plin 20 mg/m2 (Plin+Peg; n=16). Grade (Gr) 3/4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was calculated from absolute neutrophil counts obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire. Percentage of pts with RDI &lt;85% and adverse event rate (Grades 1-5) was calculated.
Results: Gr 3 or 4 neutropenia with Plin/Peg vs Peg was 50% vs 81.1% (p&lt;0.04). Median DSMN with Plin/Peg vs Peg was 0.5 day vs 1 day. ANC nadir [mean (95% CI)] with Plin/Peg vs Peg was 1.15 (0.66;1.65) vs 0.80 (0.37;1.22).
In the Plin+Peg vs Peg group, Gr 4 AE frequency was 37.3% vs 54.5%, Gr 3 AE frequency was 18.8% vs 27.3%, Gr 2 AE frequency was 25% vs 9.1% and Gr 1 AE frequency was 18.8% vs 4.5%. No Gr 5 AEs occurred in either group. Bone pain was significantly less (P&lt;0.001) with Plin+Peg vs Peg.
Conclusion: Addition of Plin to Peg has superior prevention of CIN, superior safety, superior RDI and superior protection against bone pain compared to standard dose Peg alone in this randomized phase 2 trial. A confirmatory global Phase 3 trial comparing Plin+Peg vs Peg alone is underway.
RDI&lt;85%Cycle 1Cycle 2Cycle 3Cycle 4Peg0 %13.6 %19.1 %19.1 %Plin+Peg0 %6.25 %6.25 %6.25 %
Citation Format: Douglas W. Blayney, Greg Ginn, Lan Huang, Ramon W. Mohanlal. Plinabulin and pegfilgrastim (Plin+Peg) versus peg monotherapy (Peg) after TAC: A comparison of efficacy, safety, relative dose intensity (RDI) and bone pain [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 PS11-15.