Trifluridine–tipiracil and bevacizumab in refractory metastatic colorectal cancer
Open accessAbstract
BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival. METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability). RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).
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- Authors
- Prager, G. W., Taieb, J., Fakih, M., Ciardiello, F., Van Cutsem, E., Elez, E., Cruz, F. M., Wyrwicz, L., Stroyakovskiy, D., Pápai, Z., Poureau, P.-G., Liposits, G., Cremolini, C., Bondarenko, I., Modest, D. P., Benhadji, K. A., Amellal, N., Leger, C., Vidot, L., & Tabernero, J.
- Affiliations
- University of Pisa (IT)
- From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Université Paris Cité, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) — all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) — both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d’Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau–Quiron, Barcelona (E.E., J. ...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2023-05-04
- Volume
- 388
- Issue
- 18
- Pages
- 1657-1667
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W4367835002
- Cited by
- 467
- References
- 34
- Citations by year
- 2026: 135 · 2025: 145 · 2024: 151 · 2023: 36
- FWCI
- 58.18
- Type
- journal article
- Language
- en
- Open access
- green
- pure.au.dk
- Licence
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- Taiho Oncology, Inc (N/A)
- Servier (N/A)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- trifluridine/tipiracil, bevacizumab, metastatic colorectal cancer, refractory cancer, combination chemotherapy, overall survival, progression-free survival, ECOG performance status, neutropenia, adverse events, anti-VEGF therapy, oral fluoropyrimidine, second-line therapy
- MeSH terms
- Bevacizumab, Adult, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, Drug Combinations, Humans, Pyrrolidines, Rectal Neoplasms, Thymine, Trifluridine, Uracil, Colorectal Neoplasms
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