Positioning Third-Line TKIs in mCRC

In this episode, “Positioning Third-Line TKIs in mCRC,” the panel explores how clinicians incorporate fruquintinib and regorafenib into the later-line treatment landscape. Dr. Kazmi discusses fruquintinib as a viable third-line option and describes how he chooses between it and trifluridine and tipiracil plus bevacizumab on a case-by-case basis. Baseline myelotoxicity, platelet and white blood cell counts, disease burden, metastatic pattern, and the pace of progression on prior chemotherapy may all influence treatment selection. In patients with rapid progression or short-lived responses to cytotoxic therapy, he may favor moving to fruquintinib rather than using another cytotoxic regimen. He also notes that he has not encountered significant payer barriers when prescribing the drug.

Dr. Strickler then discusses regorafenib and how its role has evolved. He attributes much of the drug’s historical toxicity to the original starting dose and highlights the ReDOS strategy, which begins at 80 mg and gradually escalates according to patient tolerance. With trifluridine and tipiracil plus bevacizumab and fruquintinib now available, the exact position of regorafenib is less clearly defined. Dr. Strickler often considers it after third-line therapy, although tolerability and access may influence sequencing. The episode emphasizes that later-line TKI selection depends on treatment history, toxicity, dosing strategy, and individual patient circumstances rather than a single fixed sequence.

The next episode in this series, “BRAF V600E mCRC: Targeted Therapy and Rechallenge Strategies,” focuses on biomarker-driven treatment and the evolving role of molecularly guided rechallenge.