Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study

Abstract

Background:We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TTeB) and capecitabine plus bevacizumab (CeB) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. Patients and methods: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TTeB (N ¼ 77) or CeB (N ¼ 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. Results: Median (range) duration of treatment was 7.8 (6.0e9.7) months and 6.2 (4.1e9.1) months in the TTeB and CeB groups, respectively. Median (range) PFS was 9.2 (7.6e11.6) and 7.8 (5.5e10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TTeB had more grade !3 neutropenia (47% versus 5% with CeB). Patients receiving CeB had more grade !3 handefoot syndrome (12% versus 0% with TTeB) and grade !3 diarrhea (8% versus 1% with TTeB), consistent with the known safety profiles of these agents. Conclusion: TTeB treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. Clinical trial information: NCT02743221 (ClinicalTrials.gov)

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

“…For example, a Phase III trial (SOLSTICE) is currently investigating the efficacy and safety of FTD/TPI plus bevacizumab (versus capecitabine plus bevacizumab) in the first-line treatment of mCRC in patients who are not eligible for intensive chemotherapy [28]. This trial follows on from the Phase II TASCO1 trial, in which FTD/TPI plus bevacizumab showed promising activity in this patient group (median PFS and OS: 9.2 and 18 months, respectively) [29]. Although the efficacy results of SOLSTICE will not inform the third-line treatment of mCRC, it will generate safety and tolerability data that may facilitate decision-making across the continuum of care.…”

Long Term Real-World Outcomes of Trifluridine/Tipiracil in Metastatic Colorectal Cancer—A Single UK Centre Experience

“…Importantly, the improvement in OS will be a key consideration by funding agencies. Its role in earlier lines of treatment remains to be answered by ongoing trials [ 19 , 20 , 21 ]. Our study suggests some tumour-factors that may help select patients who would most benefit from Lonsurf.…”

Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group

“…The TASCO1 study is a phase II randomised open-label noncomparative study assessing safety and efficacy (PFS, primary outcome) of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with mCRC not candidates for standard oxaliplatin- or irinotecan-based chemotherapy regimens. Median PFS was 9.2 (95% CI, 7.6–11.6) and 7.8 (95% CI, 5.5–10.1) months in the TT-B and C-B groups, respectively [ 49 ]. At ASCO-GI 2021, authors presented the median OS which was 22.31 months in TT-B and 17.67 months in C-B with HR 0.78 (95% CI, 0.5–1.10).…”