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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The most common side effects of aflibercept include GI symptoms (e.g., abdominal pain, aphthous stomatitis, diarrhea, and decreased appetite), blood disorders (e.g., thromboembolic events and neutropenic infection), hypertension, dehydration, dysphonia, dyspnea, hemorrhage, fistula formation, and impaired wound healing. It is recommended that patients should be monitored for appearance of febrile neutropenia and cardiovascular disease.
Colorectal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Two new agents with anti-angiogenesis activity gained registration after 2012 for second-line use with FOLFIRI chemotherapy after positive results from large-scale (Phase III) randomized studies as alternatives to bevacizumab. Aflibercept was the most attractive in principle of all the VEGF inhibitors because of its wide-ranging activity in multiple parts of the angiogenesis pathway. Aflibercept is formed from the fusion protein of key domains from human VEGF receptors 1 and 2 with human IgG Fc1 and blocks all human VEGF-A isoforms, VEGF-B, and placental growth factor (PlGF)-2; indeed, at such high affinity that it binds VEGF-A and PlGF more tightly compared with the native receptors. Mechanistically, aflibercept is a VEGF trap as opposed to a pure VEGF ligand inhibitor such as bevacizumab. The Phase III VELOUR study of aflibercept and FOLFIRI in second line (after failure of an oxaliplatin regimen) showed a significant survival advantage, even in patients showing resistance after prior bevacizumab exposure. However, it has a more toxic profile than bevacizumab and so has gradually fallen out of favor. The second agent, ramicirumab, is more specific for VEGF-R2 inhibition and also demonstrated survival advantage in a Phase 3 study with FOLFIRI in second line and is very well tolerated, like bevacizumab.
Colorectal cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Two new agents with broader anti-angiogenesis activity have recently (2012) gained registration, after positive results from large-scale (phase III) randomized studies. Regorafenib, an oral multi-kinase inhibitor, has shown a significant survival advantage, after failure of all known chemotherapy (i.e. in the salvage setting), compared to BSC in the CORRECT trial. Similarly, and more impressively, the phase III ‘VELOUR’ study of aflibercept and FOLFIRI, in second line (after failure of an oxaliplatin regimen), also showed a significant survival advantage, even in patients showing resistance to prior bevacizumab exposure. Aflibercept is formed from the fusion protein of key domains from human VEGF receptors 1 and 2 with human IgG Fc1 and blocks all human VEGF-A isoforms, VEGF-B and placental growth factor (PlGF)-2, indeed at such high affinity that it binds VEGF-A and PlGF more tightly compared to the native receptors. Mechanistically, aflibercept is a VEGF trap, as opposed to a pure VEGF ligand inhibitor such as bevacizumab.
Multiple Evanescent White Dot Syndrome and Choroidal Neovascularization following SARS-COV-2 Infection in a Patient on Dabrafenib and Trametinib
Published in Ocular Immunology and Inflammation, 2023
Beatrice Gallo, James S. Talks, Ranjeet J. Pandit, Andrew C. Browning
The patient underwent six monthly aflibercept injections. Five months after the presentation the white dots had disappeared (Figures 3a,b). SD-OCT demonstrated subfoveal hyperreflectivity and persistent EZ, ELM and IZ disruption/loss and disappearance of the intraretinal cysts (Figure 3c). On OCT-A no CNV was visible (Figure 3d), and both the hyperfluorescent areas on FFA and the hypofluorescent spots on ICGA had resolved (Figures 3e,f). ffERG was repeated after 6 months and demonstrated improved generalised cone photoreceptor function of the affected eye, however this was still slightly attenuated compared to the fellow eye (Figures 2c,d). At nine months from presentation the BCVA of the RE was 6/48, macular exudation was replaced by fibrosis and no new inflammatory lesions were detected in either eye.
Safety and efficacy review of aflibercept for the treatment of metastatic colorectal cancer
Published in Expert Opinion on Drug Safety, 2022
David K. Lau, Justin Mencel, Ian Chau
Anti-angiogenic therapy is an important component of systemic chemotherapy in the management of mCRC. Based upon results of the VELOUR clinical trial, aflibercept is approved for use in combination with FOLFIRI chemotherapy following failure of a first-line oxaliplatin-containing regimen regardless of prior bevacizumab exposure. Cardiovascular adverse events were the most common side effects attributable to aflibercept observed in the VELOUR study. Prospective and retrospective real-world studies have reported similar frequency of toxicity and efficacy. Since its approval for usage, rarer side effects of aflibercept have also been reported. Due to the potential for severe morbidity and mortality, it is imperative for clinicians to identify toxicities early for optimal patient management.
Up-to-date role of aflibercept in the treatment of colorectal cancer
Published in Expert Opinion on Biological Therapy, 2021
Nadia Saoudi Gonzalez, Francesc Salvà, Javier Ros, Iosune Baraibar, David Marmolejo, Augusto Valdivia, Jose Luis Cuadra-Urteaga, Nuria Mulet, Josep Tabernero, Elena Élez
Van Cutsem et al. enrolled 38 patients (61% with mCRC) in a dose-escalation phase I trial conducted in Belgium and France with intravenous aflibercept at 2, 4, 5, or 6 mg/kg on day 1, followed by irinotecan, 5-fluorouracil, and leucovorin on days 1 and 2 every 2 weeks [33]. No DLTs were reported in patients treated with 2 mg/kg dose level. Eight patients were treated then with 4 mg/kg of aflibercept. Two of these eight patients experience a DLT: proteinuria lasting >2 weeks and acute nephrotic syndrome with thrombotic microangiopathy. Four patients were enrolled at aflibercept 5 mg/kg, and two DLT with 5 mg/kg and three with 6 mg/kg were considered related to chemotherapy and underlying cancer. The most common grade 3 and 4 adverse events were neutropenia, hypertension, and diarrhea. In total, 22 patients had stable disease (SD), lasting more than 3 months in 17 patients. 9 patients experienced a partial response, mainly at 4 mg/kg dose, 6 of them with mCRC.