Regorafenib Plus Modified FOLFOX6 Does Not Boost Metastatic CRC Objective Response Rate

Adding regorafenib to a modified FOLFOX6 regimen fails to improve the objective response rate for patients with metastatic colorectal cancer

medwireNews: Combining the oral multikinase inhibitor regorafenib with a modified FOLFOX6 chemotherapy regimen does not boost the objective response rate (ORR) for patients with metastatic colorectal cancer (CRC), research suggests.

During the open-label phase II CORDIAL trial of the combined first-line treatment, 53 patients received at least one dose of regorafenib 160 mg once daily, with a median overall treatment duration of 7.7 months for regorafenib and 9.9 months for any component of the study treatment.

The ORR was 43.9%, entirely composed of partial responses, and was not superior to the ORR of 35.0% to 55.0% that has previously been achieved for metastatic CRC patients given a modified FOLFOX6 regimen alone.

Thus, the CORDIAL trial did not achieve its primary endpoint, say Fortunato Ciardiello, from Seconda Universita degli studi di Napoli in Italy, and co-authors in the European Journal of Cancer.

Median progression-free survival (PFS) for the combined regimen was 8.5 months and again this was comparable to historical reports of 8.0 and 8.5 months for patients given first-line FOLFOX or FOLFIRI chemotherapy alone, respectively.

However, the researchers note that this PFS “appeared to be longer than that in most trials investigating chemotherapy and kinase inhibitor combinations” and suggest this indicates a slowing of tumour growth in the patients.

Indeed, five patients continued with regorafenib, alone or alongside fluorouracil , for more than 6 months after the data cut off, which the team says is a “relatively long duration of treatment” when compared with other phase III trials of metastatic CRC first-line treatments.

This prompts the authors to suggest that “it would be interesting to explore the hypothesis that the addition of regorafenib to standard treatment might help patients to continue on treatment, and thus maintain tumour control for longer than might be achieved with chemotherapy alone.”

They conclude: “Characterisation of patients who could derive the most long-term benefit, and the impact of dose modifications on tolerability and treatment duration, might provide the groundwork for investigation of the use of regorafenib as maintenance therapy in patients with metastatic CRC who have achieved a clinical response to cytotoxic chemotherapy.”


Argilés G, Saunders MP, Rivera F, et al. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial. Eur J Cancer 2015; Advance online publication 25 March. DOI:

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