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Cancers
Special Issues
Real-World Evidence and Emerging Therapeutic Strategies in Refractory Metastatic Colorectal...
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Real-World Evidence and Emerging Therapeutic Strategies in Refractory Metastatic Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Metastasis".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 166

Special Issue Editor

Dr. Carlo Signorelli

E-Mail Website
Guest Editor
Medical Oncology Unit, Department of Oncology and Hematology, S. Rosa Hospital, 01100 Viterbo, Italy
Interests: colorectal cancer; gastrointestinal cancers; palliative care; refractory metastatic colorectal cancer; real-world studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Managing metastatic colorectal cancer (mCRC) refractory to conventional treatments remains a significant clinical concern. Treatment options are guided by randomized trials, but real-world evidence is crucial for evaluating results in various patient populations. The effectiveness, safety, and practical use of treatments for treatment-refractory mCRC is the focus of this Special Issue. Third-line and later-line options, such as immunotherapy, anti-angiogenics, anti-EGFR rechallenge, and targeted treatments, are the subject of accepted original research articles, retrospective or prospective cohort studies, case series, and reviews. Research on patient selection, prognostic biomarkers, and molecular profiling is particularly encouraged. By collecting these findings, we will close the gap between clinical trials and routine oncology practice, supporting individualized, evidence-based treatment strategies for advanced colorectal cancer.

Dr. Carlo Signorelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • real-world evidence
  • refractory metastatic colorectal cancer
  • treatment resistance
  • third-line and beyond therapies
  • targeted therapies
  • immunotherapy
  • patient outcomes
  • clinical practice
  • biomarkers
  • precision oncology

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Published Papers (1 paper)

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Research

20 pages, 2533 KiB  
Article
Redefining the Use of Regorafenib and Trifluridine/Tipiracil Without Bevacizumab in Refractory Metastatic Colorectal Cancer: Findings from the ReTrITA Study
by Carlo Signorelli, Maria Alessandra Calegari, Annunziato Anghelone, Alessandro Passardi, Chiara Gallio, Alessandro Bittoni, Jessica Lucchetti, Lorenzo Angotti, Emanuela Di Giacomo, Ina Valeria Zurlo, Cristina Morelli, Emanuela Dell’Aquila, Adele Artemi, Donatello Gemma, Alessandra Emiliani, Marta Ribelli, Domenico Cristiano Corsi, Giulia Arrivi, Federica Mazzuca, Federica Zoratto, Mario Giovanni Chilelli, Marta Schirripa, Francesco Schietroma, Maria Grazia Morandi, Fiorenza Santamaria, Manuela Dettori, Antonella Cosimati, Rosa Saltarelli, Alessandro Minelli, Emanuela Lucci-Cordisco and Michele Bassoadd Show full author list remove Hide full author list
Cancers 2025, 17(12), 2037; https://doi.org/10.3390/cancers17122037 - 18 Jun 2025
Viewed by 56
Abstract
Background: 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 [...] Read more.
Background: 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. Methods: 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 (n = 261), sequential R/T (n = 155), R monotherapy (n = 313), and T monotherapy (n = 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. Results: The monotherapy cohorts showed no significant difference in OS (R: 5.0 months; T: 5.9 months; p = 0.8371) or PFS (R: 3.2 months; T: 3.3 months; p = 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; p = 0.0004), and median PFS was 11.5 vs. 8.5 months (HR = 0.60; p < 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. Conclusions: 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. Full article
(This article belongs to the Special Issue Real-World Evidence and Emerging Therapeutic Strategies in Refractory Metastatic Colorectal Cancer)
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