Treatment guidelines for patients with metastatic colorectal cancer

In this report, the European Society for Medical Oncology (ESMO) updated recommendations for treating metastatic (spread to other organs) colorectal cancer.

Colorectal cancer is one of the most common cancers diagnosed in Europe. Over the last decade in particular, the clinical outcome for patients with metastatic colorectal cancer has improved. However, it is not clear which improvements in treatment have been most responsible for the improved outcomes. In late 2014, the ESMO met to offer updated recommendations for the treatment of metastatic colorectal cancer based on the recent improvements in therapy.

These guidelines were prepared by a panel of experts in colorectal cancer treatment.

Testing for mutations (permanent change) in the RAS and BRAF genes should be carried out on all patients at the time of diagnosis of metastatic colorectal cancer. RAS testing is mandatory before treatment with cetuximab (Erbitux) or panitumumab (Vectibix).

For patients with a small number of metastatic sites, systemic treatment (chemotherapy) is the standard. Chemotherapy should be considered as the initial part of every treatment strategy (with the exception of patients with liver or lung metastasis). Other treatments, such as surgery or radiation, should also be considered, depending on the location of the metastasis. Local ablation methods are possible in patients with single metastasis to the liver or lung that cannot be surgically removed. These methods remove tumor cells by thermal and/or radiation techniques.

In patients with an operable metastasis with favorable risk factors, treatment prior to surgery may not be needed. In patients with operable metastasis where the prognosis is not clear, combined chemotherapy should be given (FOLFOX or CAPOX chemotherapies). Decision making should include patients’ characteristics and preferences.

In patients with potentially operable tumors, a treatment leading to high response rates and/or large tumor shrinkage is recommended. For example, one trial found surgical removal was possible in 29% of patients following treatment with a combination chemotherapy together with cetuximab. Surgery was possible in 13% following chemotherapy alone.

The standard first-line treatments are biologicals. These treatments target different methods of tumor growth. Bevacizumab (Avastin) should be used in combination with the chemotherapies FOLFOX/CAPOX/FOLFIRI. Cetuximab or panitumumab should be used in combination with FOLFOX or FOLFIRI.

Patients treated with FOLFOX or CAPOX plus bevacizumab should be considered for maintenance therapy after 6 cycles of CAPOX or 8 cycles of FOLFOX. The optimal maintenance therapy is a combination of a fluoropyrimidine (such as Efudex) and bevacizumab. Patients receiving FOLFIRI should continue the therapy as long as the tumor continues to shrink and the treatment remains tolerable.

Second-line therapy should depend on the first-line treatment. For patients who did not receive bevacizumab as a first-line treatment, bevacizumab or aflibercept should be considered. If it was used as a first-line treatment, then aflibercept or ramucirumab (combined with FOLFIRI) should be used in the second-line.

In third-line therapy cetuximab and panitumumab should be considered in patients without RAS and BRAF mutations.

These ESMO guidelines have been developed based on the current evidence to assist in the treatment and management of disease.