Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer

Abstract

BackgroundA previous phase I/II C-TASK FORCE study of trifluridine/tipiracil plus bevacizumab for patients with heavily pretreated metastatic colorectal cancer (mCRC) showed promising activity with an acceptable toxicity profile. This retrospective study aimed to investigate the safety and efficacy of trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC in clinical settings.MethodsRecords of patients with mCRC refractory to standard therapies who initiated trifluridine/tipiracil plus bevacizumab from January 2016 to March 2018 or trifluridine/tipiracil monotherapy from June 2014 to December 2015 were retrospectively reviewed at our institution.ResultsTotally, 60 patients received trifluridine/tipiracil plus bevacizumab and 66 received trifluridine/tipiracil monotherapy. All patients had previously received standard chemotherapy. Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 2.3–5.1] in the trifluridine/tipiracil plus bevacizumab group and 2.2 months (95% CI, 1.8–2.6) in the trifluridine/tipiracil monotherapy group [hazards ratio (HR) 0.69; 95% CI 0.48–0.99]. PFS rate at 16 weeks was 46.6% for the trifluridine/tipiracil plus bevacizumab group and 33.9% for the trifluridine/tipiracil monotherapy group. Although a relatively higher incidence of grade ≥ 3 neutropenia was observed in the trifluridine/tipiracil plus bevacizumab group than that in the other group (50.0% vs. 40.9%, p = 0.371), the incidence of febrile neutropenia was not high (3.3% vs. 7.8%, p = 0.444).ConclusionsIn real-world settings, trifluridine/tipiracil plus bevacizumab prolonged PFS and helped achieve higher 16-week PFS rate compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC with manageable toxicities.Trial registrationRetrospectively registered.

Survival Benefit of Crossover Administration of Regorafenib and Trifluridine/Tipiracil Hydrochloride for Patients With Metastatic Colorectal Cancer: Exploratory Analysis of a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study (REGOTAS)

“…However, while making these active agents available is a valuable treatment strategy, the OS of these patients remains unsatisfactory and warrants further improvement. A promising efficacy of TFTD with bevacizumab was previously reported in a phase I-II trial (C-task force) (16), and was recently replicated in retrospective and prospective studies (17,18). In addition, the combination of REG with nivolumab showed manageable toxicities and encouraging antitumor activity in microsatellite stable mCRC patients (19).…”

A Comparison of Bevacizumab Plus TAS-102 and TAS-102 Monotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

“…In the end, we eliminated those single-arm studies, studies with missing efficacy evaluation data, and studies with control groups that did not meet the requirements. A total of 3 studies were included in this metaanalysis (17)(18)(19). These studies compared the efficacy and safety of bevacizumab combined with TAS-102 versus TAS-102 as a single agent in mCRC.…”

“…Among the 3 cohort studies included, 2 were single-center retrospective studies ( 17 , 19 ), and once was a multi-center, prospective, phase II randomized controlled trial (RCT) ( 18 ). For retrospective studies, we use the NOS to assess methodological quality.…”

Super-Enhancers in the Regulation of Gene Transcription: General Aspects and Antitumor Targets

“…In the culture of chronic myeloid leukemia cells, senexin B increased the antitumor effect of targeted inhibitors of chimeric tyrosine kinase Bcr-ABL [ 78 ], thus broadening the possibilities of CDK8/19 inhibition in the therapy of blood cancers. The outcomes with chemotherapy for colorectal cancer (especially metastatic disease [ 79 , 80 ]) remain unsatisfactory; therefore, the results of studies focused on this tumor and demonstrating the effectiveness of an inactivation of the Mediator complex components seem rather promising [ 29 , 32 , 81 ].…”