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

Abstract

•More effective treatment options are needed in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy.•Trifluridin/tipiracil in monotherapy and in combination is an effective and well-tolerated option in mCRC.•Trifluridin/tipiracil plus bevacizumab is active and safe for patients with mCRC ineligible for first-line combination chemotherapy. BackgroundWe designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT–B) and capecitabine plus bevacizumab (C–B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies.Patients and methodsFrom 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT–B (N = 77) or C–B (N = 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.ResultsMedian (range) duration of treatment was 7.8 (6.0–9.7) months and 6.2 (4.1–9.1) months in the TT–B and C–B groups, respectively. Median (range) PFS was 9.2 (7.6–11.6) and 7.8 (5.5–10.1) 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 TT–B had more grade ≥3 neutropenia (47% versus 5% with C–B). Patients receiving C–B had more grade ≥3 hand–foot syndrome (12% versus 0% with TT–B) and grade ≥3 diarrhea (8% versus 1% with TT–B), consistent with the known safety profiles of these agents.ConclusionTT–B 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 informationNCT02743221 (ClinicalTrials.gov) We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT–B) and capecitabine plus bevacizumab (C–B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT–B (N = 77) or C–B (N = 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. Median (range) duration of treatment was 7.8 (6.0–9.7) months and 6.2 (4.1–9.1) months in the TT–B and C–B groups, respectively. Median (range) PFS was 9.2 (7.6–11.6) and 7.8 (5.5–10.1) 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 TT–B had more grade ≥3 neutropenia (47% versus 5% with C–B). Patients receiving C–B had more grade ≥3 hand–foot syndrome (12% versus 0% with TT–B) and grade ≥3 diarrhea (8% versus 1% with TT–B), consistent with the known safety profiles of these agents. TT–B 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.

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