<p>Optimizing sequential treatment with anti-EGFR and VEGF mAb in metastatic colorectal cancer: current results and controversies</p>

Abstract

Anti-EGFR mAb (cetuximab or panitumumab) and anti-VEGF mAb (bevacizumab) are the two main targeted agents available for RAS wild-type (WT) metastatic colorectal cancer (mCRC) treatment. Nonetheless, three head-to-head clinical trials evaluating anti-EGFR mAb vs -VEGF mAb in first-line treatment failed to conclude a uniform result. Recently, a few small clinical studies revealed that prior use of bevacizumab may impair the effect of cetuximab or panitumumab. Preclinical studies have also suggested that pretreatment with bevacizumab may lead to simultaneous resistance to anti-EGFR mAb. Therefore, we performed this review to summarize the available data regarding the optimal sequential treatment of anti-EGFR and -VEGF mAb for RAS or KRAS WT mCRC and discuss the potential mechanisms that may explain this phenomenon. Primary tumor location and early tumor shrinkage have emerged as new potential prognostic and predictive factors in mCRC. We also collected information to explore whether these factors affect the optimal sequencing of targeted therapy in mCRC. However, definite conclusions cannot be made, and we can only speculate on optimal treatment recommendations based on the contradictory results.

Signaling pathways involved in colorectal cancer progression

“…Colorectal cancer cells directly could be affected by EGFR-targeting drugs as accumulating drug resistance mutations in the RAS–RAF–MEK–ERK pathway affects these cells [65]. The main agent available for RAS wild-type (WT) metastatic colorectal cancer (mCRC) treatment is anti-EGFR mAb such as cetuximab or panitumumab [66]. Moreover, panitumumab is a fully human mAb with the properties similar to cetuximab [67].…”

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

“…Colorectal cancer (CRC), the most common malignancies of digestive system, is the fourth deadliest cancer in the world, accounting for about 881,000 deaths worldwide in 2018. Most CRCs are characterized by an orderly carcinogenic process in which mutations accumulate over an average of 10 to 15 years (5,6).…”

Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

“…To date, limited data are available on mCRC patients receiving aflibercept after an anti-EGFR based-treatment and no head-to-head comparative trials have been conducted to assess which is the best anti-angiogenic agent in this specific treatment setting. As a consequence, and clinical practice is essentially based on speculations deriving from first-line studies ( 93 , 94 ). The retrospective SLAVE study evaluated the effectiveness of second-line bevacizumab-based or aflibercept-based regimens in 277 RAS WT mCRC patients progressing after a first-line anti-EGFR based treatment in a multicenter real-world cohort ( 95 ).…”