Redefining the Use of Regorafenib and Trifluridine/Tipiracil Without Bevacizumab in Refractory Metastatic Colorectal Cancer: Findings from the ReTrITA Study

<i>Background:</i> Regorafenib (R) and trifluridine/tipiracil (T) are approved treatments for metastatic colorectal cancer (mCRC) in refractory cases. However, the optimal sequencing of these agents is unknown. The ReTrITA study planned to assess the real-world efficacy of R and T, administered either sequentially or as monotherapy, in a large Italian multicentre population. <i>Methods:</i> This retrospective observational analysis comprised 1156 mCRC patients treated between 2012 and 2023 at 17 Italian cancer centres. Patients were divided into four groups: sequential T/R (<i>n</i> = 261), sequential R/T (<i>n</i> = 155), R monotherapy (<i>n</i> = 313), and T monotherapy (<i>n</i> = 427). The primary objectives were overall survival (OS) and progression-free survival (PFS), with secondary goals being disease control rate, objective response rate, and treatment-related toxicity. <i>Results:</i> The monotherapy cohorts showed no significant difference in OS (R: 5.0 months; T: 5.9 months; <i>p</i> = 0.8371) or PFS (R: 3.2 months; T: 3.3 months; <i>p</i> = 0.6531). Compared to T/R, the sequential R/T group had significantly better outcomes: median OS was 16.6 vs. 12.6 months (HR = 0.67; <i>p</i> = 0.0004), and median PFS was 11.5 vs. 8.5 months (HR = 0.60; <i>p</i> < 0.0001). The survival advantage of R/T was consistent across clinical subgroups. The toxicity profiles were comparable with known safety data, with a lower prevalence of neutropenia reported in the R/T sequence. <i>Conclusions:</i> ReTrITA confirms the efficacy of R and T as monotherapies and provides compelling real-world evidence that the R/T sequence improves survival in refractory mCRC. These findings support a regorafenib-first approach in patients who are eligible, and they emphasise the need for future research into combination strategies and comparisons with newer drugs such as fruquintinib.

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Journal
Cancers
Published
2025-06-18
DOI
https://doi.org/10.3390/cancers17122037
Citations
2
Primary Topic
Colorectal Cancer Treatments and Studies
Type
article
Field-Weighted Citation Impact
2.09
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article

Redefining the Use of Regorafenib and Trifluridine/Tipiracil Without Bevacizumab in Refractory Metastatic Colorectal Cancer: Findings from the ReTrITA Study

Emanuela Dell’Aquila, Manuela Dettori, Michele A. Basso, Federica Mazzuca et al.
2 citations
Cancers
Colorectal Cancer Treatments and Studies
2.09
article

Redefining the Use of Regorafenib and Trifluridine/Tipiracil Without Bevacizumab in Refractory Metastatic Colorectal Cancer: Findings from the ReTrITA Study

Emanuela Dell’Aquila, Manuela Dettori, Michele A. Basso, Federica Mazzuca, Maria Alessandra Calegari, Ina Valeria Zurlo, Adele Artemi, Annunziato Anghelone, Emanuela Lucci‐Cordisco, Alessandro Bittoni, Marta Ribelli, Antonella Cosimati, Marta Schirripa, Jessica Lucchetti, Maria Grazia Morandi, Domenico Corsi, Donatello Gemma, Federica Zoratto, Francesco Schietroma, Carlo Signorelli, Alessandro Minelli, Giulia Arrivi, Lorenzo Angotti, Chiara Gallio, Fiorenza Santamaria, Alessandra Emiliani, Rosa Saltarelli, Alessandro Passardi, Mario Giovanni Chilelli, Cristina Morelli, Emanuela Di Giacomo
article en
2 citations

Abstract

<i>Background:</i> Regorafenib (R) and trifluridine/tipiracil (T) are approved treatments for metastatic colorectal cancer (mCRC) in refractory cases. However, the optimal sequencing of these agents is unknown. The ReTrITA study planned to assess the real-world efficacy of R and T, administered either sequentially or as monotherapy, in a large Italian multicentre population. <i>Methods:</i> This retrospective observational analysis comprised 1156 mCRC patients treated between 2012 and 2023 at 17 Italian cancer centres. Patients were divided into four groups: sequential T/R (<i>n</i> = 261), sequential R/T (<i>n</i> = 155), R monotherapy (<i>n</i> = 313), and T monotherapy (<i>n</i> = 427). The primary objectives were overall survival (OS) and progression-free survival (PFS), with secondary goals being disease control rate, objective response rate, and treatment-related toxicity. <i>Results:</i> The monotherapy cohorts showed no significant difference in OS (R: 5.0 months; T: 5.9 months; <i>p</i> = 0.8371) or PFS (R: 3.2 months; T: 3.3 months; <i>p</i> = 0.6531). Compared to T/R, the sequential R/T group had significantly better outcomes: median OS was 16.6 vs. 12.6 months (HR = 0.67; <i>p</i> = 0.0004), and median PFS was 11.5 vs. 8.5 months (HR = 0.60; <i>p</i> < 0.0001). The survival advantage of R/T was consistent across clinical subgroups. The toxicity profiles were comparable with known safety data, with a lower prevalence of neutropenia reported in the R/T sequence. <i>Conclusions:</i> ReTrITA confirms the efficacy of R and T as monotherapies and provides compelling real-world evidence that the R/T sequence improves survival in refractory mCRC. These findings support a regorafenib-first approach in patients who are eligible, and they emphasise the need for future research into combination strategies and comparisons with newer drugs such as fruquintinib.

CancersVol. 17(12)
University of Rome Tor Vergata (IT), Policlinico Umberto I (IT), Agostino Gemelli University Polyclinic (IT), Accademia di Belle Arti di Frosinone (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda Sanitaria Locale Viterbo (IT), Ospedale San Paolo (IT), Ospedale Santa Maria Goretti (IT), Campus Bio Medico University Hospital (IT), Ospedale Vito Fazzi (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Sapienza University of Rome (IT)
Good health and well-being
Openalex Percentile: Top 12%
Colorectal Cancer Treatments and Studies
2.09
DOIOpen Access PDFOpenAlex
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