Abstract 1709P
Background
Plin is a non-G-CSF small molecule, with anti-cancer activity, and prevents CIN as single agent and in combination with Peg. In the phase (Ph) III trial PROTECTIVE-2 (NCT03294577), the Plin+Peg combination had superior CIN preventive efficacy versus (vs) Peg alone for Grade 4 neutropenia (Gr4N) (86% vs 68% for Peg alone, p<0.0015), for days of severe neutropenia (DSN, p=0.03), absolute neutrophil count (ANC) nadir (p=0.0002) (Blayney ASCO 2021). We evaluated the impact of the observed reduction in Gr4N from 86% with Peg alone to 68% with Plin+Peg on CIN outcomes using a MA.
Methods
The MA dataset was from 36 publications (n=7314 pts) selected by the search terms Grade 4 neutropenia, severe neutropenia, chemotherapy-induced neutropenia, febrile neutropenia, infection, ANC nadir, and duration of severe neutropenia, using NCBI, PubMed, and Google Scholar databases, and the Ph2/3 Plin CIN trials (n=496 pts). In this MA dataset, the broadly accepted CIN endpoints FN, DSN, and ANC nadir which were all significant (P<0.0001) with each other. I addition, Gr4N frequency was statistically significantly correlated (P<0.0001) with each FN, DSN, ANC Nadir, Hosp and Inf. Next, we used these fitted curves to predict the CIN outcomes for the Plin/Peg combination and Peg alone, based on the observed Gr4N frequency of 68% with the Plin+Peg combination and 86% with Peg alone.
Results
Predicted CIN outcomes based on a Gr4N of 86% vs 68% for Peg alone and Plin+Peg using the exponential-based models between CIN’s clinically relevant outcomes are summarized below. Table: 1709P
| Gr4N Frequency | Mean DSN | FN rate | Hospitalization rate | Mean ANC nadir | Infection rate |
| 86% (Peg Alone) | 3.01 | 24.3 | 20.6 | 0.197 | 16.5 |
| 68% (Plin+Peg) | 1.66 | 10.1 | 8.29 | 0.395 | 8.17 |
| p-value | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
Conclusions
A reduction of Gr4N from 86% to 68% by adding Plin to Peg is not only statistically highly significant, but is also likely to be highly clinically relevant.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
BeyondSpring Pharmaceuticals Inc.
Funding
BeyondSpring Pharmaceuticals Inc.
Disclosure
D. Blayney: Financial Interests, Institutional, Funding: BeyondSpring Pharmaceuticals. L. Huang: Financial Interests, Personal and Institutional, Ownership Interest: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Royalties: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Full or part-time Employment: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Stocks/Shares: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Sponsor/Funding: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Leadership Role: BeyondSpring Pharmaceuticals. R. Mohanlal: Financial Interests, Personal and Institutional, Full or part-time Employment: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Leadership Role: BeyondSpring Pharmaceuticals; Financial Interests, Personal and Institutional, Stocks/Shares: BeyondSpring Pharmaceuticals. All other authors have declared no conflicts of interest.