Current Oncology (Jun 2023)

Treatment Settings and Outcomes with Regorafenib and Trifluridine/Tipiracil at Third-Line Treatment and beyond in Metastatic Colorectal Cancer: A Real-World Multicenter Retrospective Study

  • Carlo Signorelli,
  • Maria Alessandra Calegari,
  • Michele Basso,
  • Annunziato Anghelone,
  • Jessica Lucchetti,
  • Alessandro Minelli,
  • Lorenzo Angotti,
  • Ina Valeria Zurlo,
  • Marta Schirripa,
  • Mario Giovanni Chilelli,
  • Cristina Morelli,
  • Emanuela Dell’Aquila,
  • Antonella Cosimati,
  • Donatello Gemma,
  • Marta Ribelli,
  • Alessandra Emiliani,
  • Domenico Cristiano Corsi,
  • Giulia Arrivi,
  • Federica Mazzuca,
  • Federica Zoratto,
  • Maria Grazia Morandi,
  • Fiorenza Santamaria,
  • Rosa Saltarelli,
  • Enzo Maria Ruggeri

DOI
https://doi.org/10.3390/curroncol30060413
Journal volume & issue
Vol. 30, no. 6
pp. 5456 – 5469

Abstract

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Background: Patients with refractory mCRC rarely undergo third-line or subsequent treatment. This strategy could negatively impact their survival. In this setting, regorafenib (R) and trifluridine/tipiracil (T) are two key new treatment options with statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control with different tolerance profiles. This study aimed to retrospectively evaluate the efficacy and safety profiles of these agents in real-world practice. Materials and Methods: In 2012–2022, 866 patients diagnosed with mCRC who received sequential R and T (T/R, n = 146; R/T, n = 116]) or T (n = 325]) or R (n = 279) only were retrospectively recruited from 13 Italian cancer institutes. Results: The median OS is significantly longer in the R/T group (15.9 months) than in the T/R group (13.9 months) (p = 0.0194). The R/T sequence had a statistically significant advantage in the mPFS, which was 8.8 months with T/R vs. 11.2 months with R/T (p = 0.0005). We did not find significant differences in outcomes between groups receiving T or R only. A total of 582 grade 3/4 toxicities were recorded. The frequency of grade 3/4 hand-foot skin reactions was higher in the R/T sequence compared to the reverse sequence (37.3% vs. 7.4%) (p = 0.01), while grade 3/4 neutropenia was slightly lower in the R/T group than in the T/R group (66.2% vs. 78.2%) (p = 0.13). Toxicities in the non-sequential groups were similar and in line with previous studies. Conclusions: The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

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