Metastatic colorectal carcinoma (mCRC) is one of the most prevalent types of cancer worldwide. After tumor progression with first- and second-line treatment, trifluridine (FTD) and tipiracil (TPI) has been shown to be a treatment option.
Data from a pivotal phase 3 trial (RECOURSE) and an ongoing phase 3b trial (PRECONNECT) have shown that, in mCRC patients who experienced disease progression after 2 lines of standard therapy, treatment with FTD/TPI is safe and efficacious. Other third-line options include regorafenib, rechallenge with previous treatment lines or personalized approaches based on comprehensive molecular profiling. Randomized trials or sequential studies aiming for the right treatment sequence or predefined subtypes for FTD/TPI or regorafenib as well for rechallenge are missing. However, FTD/TPI as well as regorafenib are recommended by the current ESMO, German S3, and National Comprehensive Cancer Network (NCCN) guidelines in the same situation, thus offering physicians a number of alternatives for the treatment of mCRC patients after the second progression. Key Message: This narrative review summarizes published data and their impact for FTD/TPI as well for regorafenib and rechallenge chemotherapy in clinical practice settings of refractory situations of colorectal cancer.