Abstract P1-12-10: Superior Effectiveness of Plinabulin (Plin) versus No-Treatment for Docetaxel (Doc)-Induced Neutropenia (N) and other Hematologic Complication in Breast Cancer (BC) Patients
Authors: Blayney Doug , Wells Jasmine , Duprez Stephen , Legaspi Gabrielle , Huang Lan , Mohanlal Ramon 
Published: March 2023

Abstract
Introduction: Minimizing hematologic complications (HC) in breast cancer patients (pt) increases pt safety and convenience, minimizes financial toxicity and may lower risk for COVID-19 infection. Plin is a novel small molecule which protects bone marrow progenitor stem cells and is non-inferior to Peg for the prevention of chemotherapy-induced neutropenia (CIN) after Doc (Blayney, JAMA Open 2021). In contrast to pegfilgrastim (Peg), Plin (as a single dose per cycle), is given on the same day of chemotherapy, has minimal bone pain and thrombopenia, has anti-cancer efficacy, and could minimize healthcare system touches (Blayney, JAMA Onc 2020; Han, ESMO 2021). Doc 75 mg/m2 in BC pts is typically used without G-CSF prophylaxis (‘no treatment’). We evaluated Plin’s HC preventive effects in comparison to no-treatment in BC patients receiving Doc from published studies.
Methods: The HC endpoints from the 27 early BC patients with at least one NCCN high FN risk factor (N=27) from the phase 3 CIN trial (PROTECTIVE-1, NCT03102606) were compared with No-Treatment (non-prophylactic Peg or G-CSF) in patients receiving 75 mg/m2 Doc. Plin was given by 30 minute (min) IV infusion as a single dose each cycle, 30 min after Doc, over 4 cycles. Cycle 1 hematology measurements in Plin-treated pts were taken pre-dose and days 1, 2, 6, 7, 8, 9, 10, 15 and 21 (10 ANC values in cycle 1); and in cycles 2-4 on days 1, 8, 21 and at end of study and were then analyzed by Covance Central Laboratory. No treatment neutropenia data was obtained from published cancer trials with monotherapy Doc 75 mg/m2 in two No-Treatment studies with at least weekly blood sampling (Harvey et al., JCO, 2006: ~3-4 draws in cycle 1), or twice-weekly (Dieras et al., Br J Ca, 1996: ~5-6 draws in cycle 1). The HC endpoints were all grade (Gr) N, Gr4N, Gr3/4N, Gr3/4 febrile N (FN), infections, anemia and thrombopenia. Other endpoints were adverse events (AEs) and Quality of Life (QoL with EORTC QLQ-C30).
Results: Baseline demographics were generally comparable between the Plin and No-Treatment literature studies for age, ECOG, and number of prior lines. Gr4N frequency with Plin was 44%, 11%, 3% and 0% in cycles 1, 2, 3 and 4 respectively, thus no added Gr4N was observed after cycle 4. Plin had significantly less neutropenia, and numerically less anemia and thrombopenia vs No-Treatment. QoL with plinabulin remained unchanged over 4 cycles.
Conclusion: Blood sampling in the No-Treatment studies (Harvey and Dieras) were infrequent, and likely underestimated the true Gr4N frequency. Despite a higher frequency of ANC sampling in cycle 1, Plin was superior vs No-Treatment for Doc-induced neutropenia and HC, while maintaining QoL and with minimal AE and bone pain burden. The same day dosing combined with the avoidance of AEs typically leading to healthcare touches, provides a distinct benefit with Plin for the prevention of Doc-induced neutropenia.
Table: Hematologic Complications
Citation Format: Doug Blayney, Jasmine Wells, Stephen Duprez, Gabrielle Legaspi, Lan Huang, Ramon Mohanlal. Superior Effectiveness of Plinabulin (Plin) versus No-Treatment for Docetaxel (Doc)-Induced Neutropenia (N) and other Hematologic Complication in Breast Cancer (BC) Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-10.