The role of cetuximab in converting initially unresectable colorectal cancer liver metastases for resection

Abstract

In patients with metastatic colorectal cancer (mCRC) predominantly confined to the liver, whether a patient undergoes potentially curative resection of the liver lesions is a well-established principal determinant of long-term survival. There are a number of different agents, both chemotherapeutic and targeted biologic agents, which can aid in shrinking liver tumors, which would have otherwise been unresectable, allowing for potentially curative resection. The aim of this review article is to summarize the available evidence regarding optimal therapeutic strategies for converting initially unresectable metastases for potentially curative resection; we do not discuss patients who present with initially resectable disease. We have taken the approach to review trials that included R0 resection rates as one of the principal study endpoints and specifically enrolled patients with liver-limited disease. Primary tumor location has recently emerged as a putative prognostic and predictive factor in patients with mCRC; however, presently, there is a lack of resectability outcomes differentiating tumor location-defined subgroups, and several ongoing trials and retrospective analyses are anticipated to guide insights in the future. In conclusion, in patients with RAS wild-type mCRC, the data support preferential use of the anti-epidermal growth factor receptor monoclonal antibody cetuximab when combined with standard-of-care infusional doublet chemotherapy regimens (FOLFOX or FOLFIRI) for the conversion of initially unresectable metastases for potentially curative resection. Furthermore, we discuss data involving intensified chemotherapy regimens (i.e., 3-drug backbones such as FOLFOXIRI with or without a targeted biologic agent) to promote the conversion of initially unresectable metastases for potentially curative resection.

Current Treatment of Colorectal Liver Metastasis as a Chronic Disease

“…The use of biologic agents combined with doublet chemotherapy regimens (FOLFOX or FOLFIRI) increases the resectability rate for initially unresectable CRLM. Furthermore, successful conversion results in outcomes similar to initially resectable CRLM (52)(53)(54). Due to downsizing by chemotherapy, between 13% and 54% of unresectable patients become resectable (51).…”

Abnormal Liver Function Induced by Space-Occupying Lesions Is Associated with Unfavorable Oncologic Outcome in Patients with Colorectal Cancer Liver Metastases

“…Aggressive metastasectomy, combined with advancements in systemic chemotherapy, has led to significantly improved outcomes in patients with CRLM [ 18 – 20 ]. The overall 5-year survival rate for patients with resectable CRLM isolated to the liver is between 35% and 60% [ 21 , 22 ] and the median survival duration is up to 22 months with systemic chemotherapy alone [ 23 – 25 ]. Unfortunately, the vast majority (75%–80%) of patients with CRLM are deemed unsuitable for surgical resection at initial diagnosis [ 26 , 27 ]; thus, there remains a high demand for effective CRLM treatments and improved palliative results.…”

Inmunología del cáncer II: bases moleculares y celulares de la carcinogénesis

“…Debido a la relevancia en el cáncer de la familia HER, se han registrado diversas estrategias terapéuticas basadas en la inhibición de sus miembros, que incluyen TKI (32) , anticuerpos monoclonales (33)(34)(35) e inmunoterapias (36)(37) .…”