PD-010 Association between chemotherapy-induced neutropenia at 1-month and overall survival in patients receiving TAS-102 for metastatic colorectal cancer

Abstract

Introduction: Favorable outcomes have been reported in patients with several types of cancers who had chemotherapy‐induced neutropenia (CIN). TAS‐102 (trifluridine and tipiracil hydrochloride; a novel combination oral nucleoside anti‐tumor agent) was first approved in Japan on March 2014 and received US. Food and Drug Administration (FDA) approval on September 2015 after a global phase 3 RECOURSE trial in patients with metastatic colorectal cancer (mCRC). Exposure‐dependent incorporation of trifluridine as an antitumor component of TAS‐102 into DNA of tumors as well as white blood cells in preclinical model suggests CIN may serve as a potential surrogate of TAS‐102 efficacy. Methods: The purpose of this retrospective cohort study is to evaluate the association of CIN at 1‐month and outcomes in patients received TAS‐102 for metastatic colorectal cancer (mCRC). The patients who had been treated with TAS‐102 monotherapy at Mayo Clinic and Yale Cancer Center between March 2015 and September 2015 through the expanded access program (EAP) and National Cancer Center Hospital East (NCCHE) between May 2014 and September 2015 were investigated. CIN at 1‐month after starting TAS‐102 was defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as a neutrophil count decrease of ≥ grade 2 (absolute neutrophil count < 1500/mm3). The median progression‐free survival (PFS) and overall survival (OS) were calculated using the Kaplan‐Meier method, and differences were evaluated using the Log‐rank test. Landmark analysis at 1‐month from starting TAS‐102 was used in this study. Results: Among 175 patients who received TAS‐102 monotherapy at Mayo Clinic, Yale Cancer Center and NCCHE, 18 patients with less than 28 days of follow up or disease progression and eight patients without information about CIN at 1‐month were excluded. Among a total of 149 patients, 69 (46%) patients developed ≥ grade 2 CIN at 1‐month. Patients who developed ≥ grade 2 CIN at 1‐month had a both longer PFS (median 3.0 vs. 2.4 months; Log‐rank P‐value= 0.01) as well as OS (median 14.0 vs. 5.6 months; Log‐rank P value < 0.0001). Additionally, disease control rate (DCR) was relatively higher in the patients with ≥ grade 2 CIN at 1‐month (49.2% vs. 37.8%; P = 0.18). Only CIN at ≥ grade 2 at 1‐month (adjusted HR: 0.21, 95% CI: 0.11‐0.38) and higher baseline CEA levels (adjusted HR: 2.00, 95% CI: 1.22‐3.35) were independent predictors of OS. The results were consistent with between both of the cohorts from United States and Japan. Conclusion: CIN at 1‐month from starting TAS‐102 was associated with favorable outcome in patients with metastatic colorectal cancer.