Abstract P5-18-04: Combination plinabulin+pegfilgrastim (Plin+Peg) had better toxicity management and health related quality-of-life (HrQoL) compared to Peg alone in early-stage breast cancer (BC) patients (pts) treated with taxotere, doxorubicin and cyclophosphamide (TAC)
Authors: Blayney Douglas W. , Lelorier Yvette , Mitchell Dominic , Huang Lan , Mohanlal Ramon 
Published: March 2022

Introduction TAC chemotherapy may have better survival outcomes than TC or AC, but is used less often likely because of toxicity and reduced HrQoL (Fujii Jama Oncol 2005; Martin Annals of Oncol 2006). Combination Plin+Peg is superior to Peg alone for the prevention of chemotherapy-induced-neutropenia (CIN): 68% vs 86% grade (Gr) 4 neutropenia with Plin+Peg vs Peg (P=0.0015). FN rate was 3.6% vs 6.3% for Plin+Peg vs Peg. Here we analyzed the mitigating effects of Plin on toxicity and HrQoL impacted by adjuvant TAC in BC pts also receiving Peg. Methods In the randomized, double-blinded trial PROTECTIVE-2 (NCT0329457), Stage I,II,III BC pts received TAC (T dose 75mg/m2, A dose 50 mg/m2, C dose 500 mg/m2) with either the Plin+Peg combination (n=110) or Peg alone (n=111) for 4 cycles. Toxicity was evaluated by central laboratory (Covance) hematology and chemistry assessments, AE collection and 12-lead ECG. HrQoL was assessed by EORTC QLQ-C30 and EQ-5D-5L. pCR rate was assessed by pathological evaluation of excised BC tissue after surgery. Pts with abnormal cardiac function meeting any of the following criteria were excluded: 1. Prior doxorubicin (&gt;240 mg/m2) or anthracycline exposure; 2. Cardiac ventricular dysfunction; 3. LVEF≤50%; 4. Congestive heart failure of NYHA Class II,III, IV cardiac disease; 5. History of myocardial infarction or coronary artery disease; 6. ECG findings consistent with active ischemic heart disease; angina pectoris requiring medication; 7. Arrhythmia requiring medication; severe conduction anomaly; 8. History of congenital QT prolongation; 9. Significant cardiac valvular disease; 10. Uncontrolled hypertension. Plin 40 mg fixed dose was given on day 1 (the day of TAC administration), and peg 6mg was given on day 2. Results All grade (Gr) AE frequency was 97% vs 96% in Plin+Peg vs Peg. However a shift to lower grade was noted. Gr 4 AE frequency was lower with Plin+ Peg vs Peg: 59% vs 80% (p&lt;0.03). Gr3 (18% vs 6%) and Gr 2 (19% vs 9%) frequency was higher with Plin+Peg vs Peg. EQ-5D-5L utility values over all cycles had slightly increased with Plin+Peg, but steadily decreased with Peg alone (see table); Day -1 represent the score on the date before TAC dosing. ⋯add more HrQoL data⋯.pCR rates was numerically higher with Plin+Peg vs Peg (13.04% vs 12.5%). No cardiac dysfunction-related AEs were noted with Plin+Peg or Peg.

Conclusion The addition of Plin to Peg for CIN prevention enables better management of TAC induced toxicity and HrQoL. TAC should be reevaluated in early stage BC patients in light of the improved outcomes with Plin+Peg support.

EQ-5D-5L Utility values*+Cycle 1 Day -1Cycle 2 Day -1Cycle 3 Day -1Cycle 4 Day -1Plin +Peg (n=109)0.930.950.930.92Peg (n=106)0.930.910.890.87*p=0.0245 for Plin+Peg vs Peg favoring Plin+Peg +United States Valuation of EQ-5D-5L Health States Using (Pickard 2019).

Citation Format: Douglas W. Blayney, Yvette Lelorier, Dominic Mitchell, Lan Huang, Ramon Mohanlal. Combination plinabulin+pegfilgrastim (Plin+Peg) had better toxicity management and health related quality-of-life (HrQoL) compared to Peg alone in early-stage breast cancer (BC) patients (pts) treated with taxotere, doxorubicin and cyclophosphamide (TAC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-04.