Rechallenge with folfox or folfiri in later lines of treatment for metastatic colorectal cancer: insights from real-world data

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The treatment for unresectable metastatic CRC in initial lines involves chemotherapy regimens such as FOLFOX or FOLFIRI, combined or not with anti-EGFR or anti-VEGF therapy, depending on RAS/BRAF status. Following disease progression, minimal benefit is observed with Regorafenib or Trifluridine-Tipiracil. In later lines, the rechallenge strategy involving 5-FU-based chemotherapy is frequently employed in clinical practice, although its efficacy remains uncertain in the literature.

Objective: The objective of this study was to investigate the outcomes of 5-FU-based chemotherapy rechallenge in later treatment lines, using real-world data from patients treated in a private clinic.

Methods: This is a retrospective analysis of patients who underwent treatment at a private medical center in Salvador, Bahia, Brazil. Data were collected from medical records between January 2015 and January 2020 to describe progression-free survival (PFS), overall survival (OS) and response rate following rechallenge therapy.

Results: During this period, 168 patients were diagnosed with metastatic CRC, and 27 were subjected to rechallenge treatment. Most of these patients (81.5%) received four or more lines of treatment. After the first evaluation, at 3 months post-rechallenge, 14.9% of the patients had an objective response, 11.1% experienced stable disease, and 74% presented with tumor progression. Among the patients who exhibited an objective response, the majority (66.7%) had oligometastatic disease and underwent some local treatment during their metastatic disease period. The patients had a median overall survival of 6 months following rechallenge therapy. Median PFS was 5 months among those who achieved an objective response compared to 3 months in those without a response (p = 0.015). Treatment-related adverse events were observed in all patients, with 37% of them classified as grade 3 or 4. One patient died during rechallenge treatment.

Conclusion: In conclusion, this analysis indicates the limited benefit of 5-FU-based chemotherapy in later lines, with a high incidence of adverse events, but potentially better outcomes in oligometastatic disease. Despite the limitations of a small sample size from a single center, this study suggests the need for further research using real-world data, which could provide insights into rechallenge therapies in colon cancer.

Corresponding author: Priscila Doria (e-mail: pg.doria@gmail.com).