National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China
Yuankai Shi , Douglas W. Blayney , Hryhorii Adamchuk , Qingyuan Zhang , Lihua Du , Lan Huang , Ramon Mohanlal
Background: PN [absolute neutrophil count (ANC) of <0.1 cells x 10E9/L)] is the most severe form of chemotherapy (Chemo)-induced neutropenia (CIN), and is associated with severe adverse clinical outcome. According to literature, PN leads to 80% death in first week of infection1, 48% FN and 50% Infection2. Peg is standard of care for the prevention of CIN. Peg has a slow onset of action with absolute neutrophil count (ANC) recovery occurring in week 2 of the cycle (C), leaving patients (pts) vulnerable in the first week of the Cycle (C), which >75% of negative clinical consequences occur. Plin, which received breakthrough designation from FDA, is a novel, non-G-CSF small molecule agent for the prevention of CIN and has CIN protection in week 1 (Blayney JAMA Onc 2020), which is the rationale for adding Plin to Peg to achieve superior protection against CIN throughout the entire cycle vs Peg alone (Blayney, St Gallen 2019; ASCO 2019). Methods: Plin is given on Day (D)1 after the last Chemo, has a favorable safety profile, and also has anticancer activity. A phase 3 study evaluating Plin as an anticancer agent (DUBLIN-3; NCT02504489) in NSCLC pts, is fully enrolled, with anti-cancer OS results expected in 2021. In PROTECTIVE-2 (Study 106; NCT0329457), we compare the CIN preventive effects of Plin (on D1) added to Peg (on D2) vs Peg alone. Here we report on PN results. Study 106 is a global multicenter randomized (1:1) double-blind study to evaluate Plin 40 mg + Peg 6mg (Arm 1) versus Peg 6mg + Plac (Arm 2) in early-stage BC (node positive or node negative with a high risk of recurrence) pts (n=221) with ECOG status 0 or 1, receiving docetaxel (75 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (TAC). Primary objective was to compare the prevention of severe (Gr 4) neutropenia between Plin+Peg and Peg+Plac. As an exploratory objective in C1, we evaluated PN between the Plin/Peg and Peg/Plac. ANC (Covance Central Laboratory) was assessed in Cycle 1 (C1) on D 1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 13, and 15. Results: Shown in the table below. Conclusions: In conclusion, Peg still cannot protect patients with the most severe form of neutropenia, PN, at 46.4% in this study. Adding Plin to Peg offers superior protection for the prevention of profound neutropenia by reducing > 50% of PN, and its clinical sequelae in FN and hospitalization as compared to Peg alone. References: 1. Bodey et al. Ann Intern Med 64(2): 328 (1966); 2. Bodey et al. Cancer 41(4): 1610 (1978). Clinical trial information: NCT03531099
Pts with PN (%) | Mean duration of PN (days) | Pts with PN and Febrile Neutropenia (%) | Pts with PN and Hospitalizations (%) | |
---|---|---|---|---|
Plin/Peg (n=111) | 21.6% | 0.34 | 4.2 | 8.3 |
Peg/Plac (n=110) | 46.4% | 0.63 | 13.7 | 11.8 |
p-value | 0.0001 | 0.0004 | 0.21 | 0.66 |
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Abstract Disclosures
2021 ASCO Annual Meeting
First Author: Ramon Mohanlal
2021 ASCO Annual Meeting
First Author: Douglas W. Blayney
2023 ASCO Annual Meeting
First Author: Douglas W. Blayney
2022 ASCO Annual Meeting
First Author: Douglas W. Blayney