Metastatic CRC after FOLFOX, FOLFIRI, and bevacizumab — what investigational options are available?
In metastatic colorectal cancer (mCRC), after the exhaustion of standard chemotherapy lines (FOLFOX, FOLFIRI) and bevacizumab, the treatment strategy is primarily determined by the tumour's molecular profile (RAS, BRAF, microsatellite status/dMMR, HER2) and general performance status. In later lines, investigational and accepted options include targeted therapies, re-challenge strategies, and specific clinical trials. The presented trials and data represent investigational options, do not constitute a general standard of care, and the median survival data (PFS, OS) reported in clinical trials are group-level results that do not guarantee survival for an individual patient.
In refractory metastatic colorectal cancer, the combination of trifluridine-tipiracil (FTD-TPI) with bevacizumab was evaluated in a randomized phase III trial (SUNLIGHT), where the combination demonstrated longer group-level survival compared with FTD-TPI given as monotherapy (median OS: 10.8 months vs. 7.5 months).
In the presence of targeted molecular alterations, such as the BRAF V600E mutation, targeted combination therapies (for example, encorafenib- and cetuximab-based regimens) represent a clinically validated therapeutic approach following progression.
In refractory patients who previously responded to earlier treatments and subsequently progressed, chemotherapy re-challenge (potentially complemented with targeted agents) represents an option that can be investigated in phase II clinical trials (for example, in the study registered under NCT03485027). In addition, trials are ongoing in specific molecular phenotypes (e.g., cetuximab-based continuation in RAS/BRAF wild-type cases in the NCT05312398 and NCT07389265 trials, or immunotherapy combined with toripalimab in pMMR/MSS tumours in the NCT07106034 and NCT06525428 phase II trials).
References
- Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer doi:10.1056/NEJMoa2214963
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- Continuation of Cetuximab Beyond First-Line Progression in Metastatic Colorectal Cancer NCT07389265
- CAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio-marker Driven Cetuximab-based Treatment Regimen NCT05312398
- Standard Systemic Therapy Combined With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer NCT06525428
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