Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting

Abstract

We evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab in treating refractory metastatic colorectal cancer (mCRC) in a retrospective, observational study. Patients refractory or intolerant to standard therapies received TAS-102 (30–35 mg/m2 twice daily on days 1–5 and days 8–12 every 28 days) plus bevacizumab 5 mg/kg on days 1 and 15. Clinical and pathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) data were collected and analysed. Thirty-five patients were treated from July 2019 to October 2021 (median age 64 years). The majority of patients (68.6%) were receiving TAS-102 plus bevacizumab as third-line treatment. Patients received a median of 4 (range 2–15) cycles of treatment. Among 31 patients evaluable for response (88.6%), ORR and DCR were 3.2% and 51.6%, respectively. After a median 11.6 months’ follow-up, median PFS was 4.3 (95% confidence interval [CI] 3.4–5.1) months and median OS was 9.3 (95% CI 6.6–12.1) months. The most common grade 3–4 toxicities were neutropenia, asthenia and nausea/vomiting, and there were no treatment-related deaths. This real-world study confirms the efficacy and safety of TAS-102 plus bevacizumab in patients with refractory mCRC.

A Systematic Review and Meta-Analysis of Trifluridine/Tipiracil plus Bevacizumab for the Treatment of Metastatic Colorectal Cancer: Evidence from Real-World Series

“…The main types of identified articles leading to exclusion were reviews, guidelines, and editorials. Ten series for potential inclusion in the meta-analysis were identified [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. After evaluation, two of the series were excluded, as they contained, based on the authors, similar centers and dates of study performance, potentially overlapping patients [ 26 , 27 ].…”

“…Among the remaining eight series, six series were from Asia (of which five series were from Japan, where trifluridine/tipiracil was initially developed, and one series from China, Table 1 ) [ 18 , 21 , 22 , 23 , 24 , 25 ]. Two series were from European centers [ 19 , 20 ]. Dates of publication were between 2020 and 2022, and a total of 441 patients were described.…”

“…This difference was not statistically significant. The other western study and the three Asian studies, that included data on the number of previous lines of therapies, did not report efficacy results according to the number of previous lines of treatment received [ 18 , 20 , 21 , 22 ]. Similarly, no data on efficacy of treatment, according to whether patients had undergone surgery for the primary site, were reported.…”

Bevacizumab mitigates codon-specific effects of trifluridine/tipiracil on efficacy outcome parameters in metastatic colorectal cancer

“…This study holds significant relevance for physicians in routine clinical practice for several reasons: (i) it represents the largest real-world dataset of patients treated with FTD/TPI + bevacizumab in routine practice in the Western world, 12 , 13 , 14 , 15 and (ii) it places a particular focus on distinct molecular subgroups.…”

Classical Angiogenic Signaling Pathways and Novel Anti-Angiogenic Strategies for Colorectal Cancer

“…Bevacizumab is an FDA-approved antiangiogenic agent targeting VEGF for the treatment of metastatic colorectal cancer (MCRC) ( Figure 1 ) ( Table 1 ) [ 36 ]. Studies have shown that the overall response rate and disease control rate of bevacizumab combination therapy in 35 CRC patients were 3.2% and 51.6%, respectively [ 37 ]. Aflibercept is also an antiangiogenic drug already in use.…”