E Van Cutsem1, I Danielewicz2, M P Saunders3, P Pfeiffer4, G Argilés5, C Borg6, R Glynne-Jones7, C J A Punt8, A J Van de Wouw9, M Fedyanin10, D Stroyakovskiy11, H Kroening12, P Garcia-Alfonso13, H Wasan14, A Falcone15, A Kanehisa16, A Egorov16, P Aubel16, N Amellal16, V Moiseenko17. 1. University Hospitals Leuven and KU Leuven, Leuven, Belgium. Electronic address: eric.vancutsem@uzleuven.be. 2. Szpitale Wojewodzkie w Gdyni/Gdansk Medical University, Gdynia, Poland. 3. Christie Hospital NHS Foundation Trust, Manchester, UK. 4. Odense University Hospital, Odense, Denmark. 5. Vall d'Hebrón Institute of Oncology and Vall d'Hebrón University Hospital, Barcelona, Spain. 6. University Hospital Besançon, Besançon, France. 7. Mount Vernon Hospital, Northwood, UK. 8. Amsterdam University Medical Centers, Amsterdam. 9. VieCuri Medisch Centrum Noord-Limburg, Venlo, The Netherlands. 10. NN Blokhin National Medical Research Center of Oncology, Moscow, Russia. 11. Moscow City Oncology Hospital N62, Moscow, Russia. 12. Schwerpunktpraxis für Haematologie und Onkologie Hasselbachplatz, Magdeburg, Germany. 13. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 14. Hammersmith Hospital, Imperial College London, London, UK. 15. University Hospital of Pisa, Department of Oncology, Pisa, Italy. 16. Institut de Recherches Internationales Servier, Suresnes, France. 17. Saint-Petersburg Scientific Practical Center for Specialized Medical Care, St Petersburg, Russia.
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 (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 METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).
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 (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 METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).
Authors: Yeong Hak Bang; Jeong Eun Kim; Ji Sung Lee; Sun Young Kim; Kyu-Pyo Kim; Tae Won Kim; Yong Sang Hong Journal: Sci Rep Date: 2021-03-29 Impact factor: 4.379
Authors: G Sommerhäuser; A Kurreck; S Stintzing; V Heinemann; L Fischer von Weikersthal; T Dechow; F Kaiser; M Karthaus; I Schwaner; M Fuchs; A König; C Roderburg; I Hoyer; M Quante; A Kiani; S Fruehauf; L Müller; A Reinacher-Schick; T J Ettrich; A Stahler; D P Modest Journal: BMC Cancer Date: 2022-07-27 Impact factor: 4.638