Targeted Therapies in Metastatic Colorectal Cancer: A Systematic Review and Assessment of Currently Available Data

Abstract

Background. Survival of patients with metastatic colorectal cancer (mCRC) has been significantly improved with the introduction of the monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel molecular-targeted agents such as aflibercept and regorafenib have recently been approved. The aim of this review is to summarize and assess the effects of molecular agents in mCRC based on the available phase II and III trials, pooled analyses, andmeta-analyses/systematic reviews. Methods. A systematic literature search was conducted using the meta-database of the German Institute of Medical Documentation and Information. Criteria of the Scottish Intercollegiate Guidelines Network were used to assess the quality of the controlled trials and systematic reviews/meta-analyses. Results. Of the 806 retrieved records, 40 publications were included. For bevacizumab, efficacy in combination with fluoropyrimidine-

The importance of optimal drug sequencing in metastatic colorectal cancer: biological rationales for the observed survival benefit conferred by first-line treatment with EGFR inhibitors

“…For example, it has previously been demonstrated that PIK3CA mutational status does not predict responsiveness to EGFR inhibitors [19,24,[84][85][86]]; however, pathway-level analyses (e.g., encompassing not only PIK3CA itself but also PTEN and other frequently mutated pathway components) are required to truly ascertain the dependency of the efficacy of EGFR-inhibitor-based therapy on the status of the PI3K/AKT/mTOR pathway. Furthermore, conflicting data exist regarding whether or not BRAF mutation predicts a lack of responsiveness to EGFR inhibitors [87]. Of potential relevance is the ongoing Phase II VISNU-2 trial, which is exploring the impact of PIK3CA and BRAF mutational status on PFS and OS in patients receiving first-line cetuximab + FOLFIRI vs bevacizumab + FOLFIRI in patients with KRAS-WT mCRC, as well as analogously designed future trials investigating additional biomarkers [88].…”

High-Value Palliative Care for Cancer Patients

“…The physical, psychological, and social costs of treatment are onerous for patients with advanced cancer, and the financial costs are particularly high; chemotherapeutic regimens frequently enter the market that are several times more expensive than similarly efficacious medicines [7]. Unfortunately, few comparative effectiveness studies exist in oncology [8], and expensive medications that provide little value over cheaper ones are depleting the financial resources of many Americans [9].…”

Improving Patient Outcomes with Regorafenib for Metastatic Colorectal Cancer - Patient Selection, Dosing, Patient Education, Prophylaxis, and Management of Adverse Events

“…To a large extent, this progress has been due to molecular targeted therapies which were first introduced in 2004. The concept and implementation of tumor growth inhibition with anti-angiogenic bevacizumab or inhibition of epidermal growth factor receptor (EGFR) signaling with cetuximab and panitumumab has substantially prolonged survival in mCRC compared to traditional chemotherapies alone [1,2,3]. With the recent approval of regorafenib (Stivarga®, Bayer HealthCare, Leverkusen, Germany), the range of treatment options for mCRC after failure of standard therapies in the first and second line has been broadened with a tyrosine kinase inhibitor (TKI) for the first time [4,5].…”