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

Abstract

Background A 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.Methods Records 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.Results Totally, 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).Conclusions In 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.

Trifluridine/Tipiracil Plus Bevacizumab for Third-Line Management of Metastatic Colorectal Cancer: SUNLIGHT Study Design

“…Although clinical trial data underpin progress in all areas of medicine, it is generally considered essential to assess how well interventions perform in everyday clinical practice. In this context, it is encouraging that a real-world study has already shown FTD/TPI plus bevacizumab to be tolerable and more effective than FTD/TPI monotherapy in the treatment of refractory mCRC [30]. In this retrospective cohort analysis, which was undertaken by the C-TASK FORCE investigators [20], FTD/TPI plus bevacizumab (n = 60) was associated with a longer median PFS compared with FTD/TPI monotherapy (n = 66; 3.7 vs 2.2 months [HR: 0.69; 95% CI: 0.48-0.99]), as well as a higher 16-week PFS rate (46.6 vs 33.9%).…”

Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

“…Therefore, the ORR may have been overestimated. Careful comparison with the results of similar studies 15,20,21 may provide suggestive evidence in support of an improved ORR with this combined drug regimen for the first‐line treatment of elderly patients in future studies.…”

“…In addition, a Phase I/II study demonstrated that FTD/TPI +Bev has favorable activity for patients with metastatic colorectal cancer who are refractory to several therapies 14 . Indeed, FTD/TPI +Bev has been already used in many clinical settings in Japan, where it has been shown to be more effective than FTD/TPI monotherapy 15 . Two randomized Phase II studies have been conducted worldwide, in which better survival was shown compared to FTD/TPI monotherapy or capecitabine +Bev 16,17 .…”

Cost-effectiveness of TAS-102 plus bevacizumab versus TAS-102 monotherapy in patients with metastatic colorectal cancer

“…Therefore, new treatment regimens for patients with mCRC are urgently needed. Recently, the clinical efficacy and safety of the combination of TAS-102 plus bevacizumab are also reported by several retrospective studies, suggesting that this regimen is potentially promising option for patients with mCRC [ 24 , 25 ]. Although the benefit of TAS-102 plus bevacizumab has not been proved clearly in a phase 3 clinical trial, this is not a sufficient ground to refrain from using TAS-102 plus bevacizumab for patients with mCRC in clinical practice.…”