1813P - The effect of increasing doses of pegfilgrastim (Peg) on thrombocytopenia (T) in breast cancer (BC) patients (pts) receiving taxotere (Doc), doxorubicin, cyclophosphamide (TAC) and plinabulin (Plin)

Abstract

BackgroundPlin is a novel non-G-CSF small molecule, in development for the prevention of Chemo-Induced Neutropenia (CIN) and is differentiated from Peg: Plin has anticancer activity, does not cause bone pain or an immune-suppressive Neutrophil profile (i.e NLR>5; Blayney ASC0 2018, ESMO 2018, SITC 2018). For Intermediate (10-20%) Risk for Febrile Neutropenia (FN) induced by Doc 75mg/m2, single agent (SA) Plin alone was equally effective vs SA Peg standard dose (6mg) for CIN. For High (> 20%) Risk FN induced by TAC, the combination of Plin with Peg 6mg was superior vs SA Peg 6mg, and Plin combined with half-dose Peg (3mg) was non-inferior, with respect to CIN (Blayney ASCO 2019; St Gallen 2019). Adding Plin to any dose of Peg eradicated Peg-induced bone pain (Blayney St Gallen 2019). Here we evaluated effects of Peg and Plin on absolute platelet count by analyzing thrombocytopenia frequency (T). MethodsWe analyzed T Grade (Gr by CTCAE 4.03 criteria) in 4 treatment arms of BC patients receiving 4 cycles of TAC and Peg doses of either 0mg (N=15), 1.5mg (N=14), 3mg (N=21) or 6mg (N=16) in the phase (Ph) II Study BPI-2358-106 (NCT03294577). All pts in these 4 arms also received Plin 20mg/m2. A 5th arm (N=22) with SA Peg 6mg (without Plin) was also evaluated for T in study 106. ResultsIncreasing Peg doses caused a statistically significant dose-dependent increase in T (Table below). T frequency with SA Plin was generally low (Table below) and not different from reported T frequency with TAC use (Any Gr T=39% and Gr3/4 T=2%; Taxotere Product Label). With SA Peg 6mg (arm 5), Gr 1 (46%), Gr 2 (5%) and Gr 3 (9%), T was not significantly (P=0.2) different vs Plin+Peg 6mg. Gr 4 T was not observed.Table1813PTableThrombocytopenia FrequencyPlin+ Peg 0mgPlin+ Peg 1.5mgPlin+ Peg 3mgPlin+ Peg 6mgP-Value of Peg Dose effect on TT Any Grade26.7%35.7%52.4%93.8%P<0.0001T Grade 120%35.7%28.6%56.3%P=0.03T Grade 26.68%0%23.8%18.8%P=0.056T Grade 30%0%0%18.8%P<0.01 ConclusionsPlin 20mg/m2 did not induce T. Peg caused a statistically and clinically significant dose-dependent increase in T. A ph III confirmatory trial is underway. Clinical trial identificationBPI-2358-106. Legal entity responsible for the studyBeyondSpring Pharmaceuticals, Inc. FundingBeyondSpring Pharmaceuticals, Inc. DisclosureD.W. Blayney: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BeyondSpring Pharmaceuticals, Inc. I. Bondarenko: Honoraria (self): BeyondSpring Pharmaceuticals, Inc. Y. Shi: Honoraria (self), Advisory / Consultancy: BeyondSpring Pharmaceuticals, Inc. S. Ogenstad: Advisory / Consultancy, Travel / Accommodation / Expenses: BeyondSpring Pharmaceuticals, Inc. L. Du: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: Wanchun Bulin Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. L. Huang: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. R. Mohanlal: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc.