Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data

Abstract

Background: Metastatic colorectal cancer (mCRC) represents a substantial health burden globally and an increasing challenge in Asian countries. Treatment options include chemotherapy plus a vascular endothelial growth factor (VEGF) inhibitor (such as bevacizumab, aflibercept or ramucirumab), or anti-epidermal growth factor receptor (EGFR) therapies. Aflibercept, a recombinant fusion protein, has been approved for treatment of mCRC in combination with FOLFIRI for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen, based on its efficacy and tolerability profile in clinical trials. This report aims to provide an overview of both clinical and real-world evidence and experience on the use of aflibercept in routine clinical practice, with a focus on European, American and Asian populations. Methods: A literature search was conducted in PubMed (on 28th February 2019) using the search terms ("aflibercept") and ("Colorectal"OR"CRC") to identify publications containing information on aflibercept-containing regimens. Results: The adverse events (AE) profile was similar between geographical locations. Across trials, real-world and retrospective studies, grade ≥ 3 hypertension and proteinuria were amongst the most frequently reported AEs. Conclusions: The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

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

“…Several retrospective and real-world studies in mCRC patients receiving FOLFIRI-aflibercept have been performed in Spain ( 111 – 117 ), France ( 118 – 120 ), the USA ( 121 ) and Asia ( 122 – 126 ). Its safety profile described in these registry and real-world studies was consistent with those reported in clinical trials; even grade ≥3 AE rates were lower in the real-life population (neutropenia: 7.7–16.2%, fatigue 6–18%, hypertension 5.6–8%), although this finding might be related to underreporting or to an improved management of patients and AEs ( 127 ). The Aflibercept Safety and health-related Quality-of-life Program (ASQoP) (NCT01571284) was a global, multicenter, single-arm, open-label study evaluating the safety and health-related QoL (HRQoL) of FOLFIRI-aflibercept in mCRC patients previously treated with an oxaliplatin-containing regimen.…”

Emerging Therapeutic Agents for Colorectal Cancer

“…Additional options independent of the KRAS mutational status are based on the VEGFR-2 targeting antibody ramucirumab or the VEGF inhibitor aflibercept. Aflibercept has been approved for treatment of mCRC in combination with FOLFIRI, a chemotherapeutic regimen including folic acid, 5-fluorouracil, and irinotecan, for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen [21]. Ziv-aflibercept is approved for the treatment of mCRC; its molecular structure is the same as that of aflibercept [22].…”

A real-world data-based safety profiling of monoclonal antibodies

“…Thyroid cancer is one of the main indications of VSP inhibitors (VEGFR-TKIs) because VEGF contributes to the occurrence and progression of thyroid malignancy greatly. However, CTs have demonstrated that VEGFR-TKIs can cause adverse events such as thyroid dysfunction (hyperthyroidism and hypothyroidism), with serious consequences that may require discontinuation of VEGFR-TKI therapy [26]. Especially, thyroid dysfunction induced by VEGFR-TKIs may be related to cancer prognosis [27].…”

“…The number of patients with metastatic colorectal cancer (mCRC) is expected to increase 60 % by 2030, reaching over 2.2 million new patients and 1.1 million deaths, which will definitely pose a tremendous health burden worldwide [26]. Although anti-angiogenesis is a valid anti-cancer strategy in most cases, some VEGFR-TKIs such as sorafenib and sunitinib performed only limited clinical benefits in the treatment of mCRC [26].…”

“…The number of patients with metastatic colorectal cancer (mCRC) is expected to increase 60 % by 2030, reaching over 2.2 million new patients and 1.1 million deaths, which will definitely pose a tremendous health burden worldwide [26]. Although anti-angiogenesis is a valid anti-cancer strategy in most cases, some VEGFR-TKIs such as sorafenib and sunitinib performed only limited clinical benefits in the treatment of mCRC [26]. As stated previously, aflibercept is distinct from other VSP inhibitors in that it functions as a decoy receptor (receptor trap) with a high affinity for angiogenic factors, placental growth factors, and VEGF.…”