Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study
Name:
36470291.pdf
Size:
368.9Kb
Format:
PDF
Description:
Identified with Open Access button
Authors
André, T.Falcone, A.
Shparyk, Y.
Moiseenko, F.
Polo-Marques, E.
Csöszi, T.
Campos-Bragagnoli, A.
Liposits, G.
Chmielowska, E.
Aubel, P.
Martín, L.
Fougeray, R.
Amellal, N.
Saunders, Mark P
Affiliation
Sorbonne University and Saint-Antoine Hospital, Department of Medical Oncology, Paris, France.Issue Date
2022
Metadata
Show full item recordAbstract
Background: Trifluridine-tipiracil plus bevacizumab has shown efficacy in previous phase 2 studies including patients with unresectable metastatic colorectal cancer. We aimed to investigate first-line trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab in patients with unresectable metastatic colorectal cancer ineligible for intensive treatment. Methods: In this open-label, randomised, phase 3 study, we enrolled patients aged 18 years and older with histologically confirmed metastatic colorectal cancer, ineligible for full-dose doublet or triplet chemotherapy and curative resection across 25 countries and regions. Participants were randomly allocated (1:1) to trifluridine-tipiracil plus bevacizumab or capecitabine plus bevacizumab until disease progression or unacceptable toxicity using an interactive web response system, stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), primary tumour location (right vs left colon), and the main reason for not being a candidate for intensive therapy (clinical condition vs non-clinical condition). The primary endpoint was investigator-assessed progression-free survival, defined as the time from randomisation to radiological progression or death from any cause, in the intention-to-treat population. Safety was assessed in all patients having taken at least one dose of the study drug. The trial is ongoing, findings presented here are those of the primary analysis of progression-free survival, conducted after 629 events had occurred. This study is registered with ClinicalTrials.gov, NCT03869892. Findings: Between March 21, 2019, and Sept 14, 2020, 856 patients (54% male, 46% female) were randomly assigned to trifluridine-tipiracil plus bevacizumab (n=426) or capecitabine plus bevacizumab (n=430). After a median follow-up of 16·6 months (95% CI 16·5-17·1), the hazard ratio for progression-free survival for trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab was 0·87 (0·75-1·02; p=0·0464; protocol-defined significance level of p=0·021 not met). Investigator-assessed median progression-free survival was 9·4 months (95% CI 9·1-10·9) with trifluridine-tipiracil plus bevacizumab versus 9·3 months (8·9-9·8) with capecitabine plus bevacizumab. The most common grade 3 and higher treatment-emergent adverse events were neutropenia (220 [52%] of 423 patients in the trifluridine-tipiracil plus bevacizumab group vs six [1%] of 427 in the capecitabine plus bevacizumab group), decreased neutrophil count (78 [18%] vs four [<1%]), anaemia (60 [14%] vs 16 [4%]), and hand-foot syndrome (none vs 61 [15%]). Nine deaths (five in the trifluridine-tipiracil plus bevacizumab group and four in the capecitabine plus bevacizumab group) were treatment related. Interpretation: First-line trifluridine-tipiracil plus bevacizumab was not superior to capecitabine plus bevacizumab in this population. As expected, the safety profile differed between the two treatments, but there were no new safety concerns. Trifluridine-tipiracil plus bevacizumab represents a feasible alternative to capecitabine plus bevacizumab in this population.Citation
André T, Falcone A, Shparyk Y, Moiseenko F, Polo-Marques E, Csöszi T, et al. Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study. The lancet Gastroenterology & hepatology. 2022 Dec 2. PubMed PMID: 36470291. Epub 2022/12/06. eng.Journal
Lancet Gastroenterology and HepatologyDOI
10.1016/s2468-1253(22)00334-xPubMed ID
36470291Additional Links
https://dx.doi.org/10.1016/s2468-1253(22)00334-xType
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/s2468-1253(22)00334-x
Scopus Count
Collections
Related articles
- TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial.
- Authors: Pfeiffer P, Yilmaz M, Möller S, Zitnjak D, Krogh M, Petersen LN, Poulsen LØ, Winther SB, Thomsen KG, Qvortrup C
- Issue date: 2020 Mar
- TRIFLURIDINE/TIPIRACIL (FTD/TPI) with or without bevacizumab in previously treated patients with esophago-gastric adenocarcinoma, a randomised phase III trial.
- Authors: Baeksgaard Jensen L, Yilmaz M, Nordsmark M, Möller S, Elle IC, Ladekarl M, Qvortrup C, Pfeiffer P
- Issue date: 2024 Apr
- Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial.
- Authors: Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Cutsem EV, Winkler RE, Makris L, Ilson DH, Tabernero J
- Issue date: 2018 Nov
- Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study.
- Authors: Van Cutsem E, Danielewicz I, Saunders MP, Pfeiffer P, Argilés G, Borg C, Glynne-Jones R, Punt CJA, Van de Wouw AJ, Fedyanin M, Stroyakovskiy D, Kroening H, Garcia-Alfonso P, Wasan H, Falcone A, Kanehisa A, Egorov A, Aubel P, Amellal N, Moiseenko V
- Issue date: 2020 Sep
- First-line trifluridine/tipiracil plus bevacizumab for unresectable metastatic colorectal cancer: SOLSTICE study design.
- Authors: André T, Saunders M, Kanehisa A, Gandossi E, Fougeray R, Amellal NC, Falcone A
- Issue date: 2020 Feb