1426 - 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)

Background

Plin 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 (3 mg) 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).

Methods

We 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 0 mg (N = 15), 1.5 mg (N = 14), 3 mg (N = 21) or 6 mg (N = 16) in the phase (Ph) II Study BPI-2358-106 (NCT03294577). All pts in these 4 arms also received Plin 20 mg/m2. A 5^th arm (N = 22) with SA Peg 6mg (without Plin) was also evaluated for T in study 106.

Results

Increasing 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 6 mg (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.Table:

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Conclusions

Plin 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 identification

BPI-2358-106.

Editorial acknowledgement

Legal entity responsible for the study

BeyondSpring Pharmaceuticals, Inc.

Funding

BeyondSpring Pharmaceuticals, Inc.

Disclosure

D.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.