Colorectal cancer
Pat Price, Karol Sikora in 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.
Polypoidal Choroidal Vasculopathy
Ching-Yu Cheng, Tien Yin Wong in Ophthalmic Epidemiology, 2022
A study conducted in Japan reported the 4-year outcome of aflibercept for nAMD and PCV, recruiting 98 AMD patients.77 During the 4 years, 25 patients dropped out. The survivors received a mean of 7.0 injections during the first year and 8.0 injections in the following 3 years. The logMAR at baseline, year 1, and year 4 was 0.28, 0.14 (P = 0.033), and 0.22 (P = 0.697), respectively. The gain of vision was not different among AMD subtypes. Among the investigated factors, the presence of external limiting membrane, the absence of vitreoretinal adhesion, and thicker choroid at baseline were associated with better logMAR values at year 4 (coefficient beta = –0.388, 0.201, and –0.001; P = 7.34 × 10–6; 0.01, and 0.028, respectively).
Approach to Retinal Vascular Disease
Anita Prasad in Laser Techniques in Ophthalmology, 2022
Location, severity of occlusion, and extent of ischaemia predict visual outcomes in RVO. Responses are variable and defining this is crucial to tailoring a patient-centric treatment regimen. Following three loading doses of anti-VEGF, the response can be categorized into: Early/good responders – CRT <250 um, patients do well long term (T&E or PRN).Partial or non-responders – CRT >250 um, further categorized as Patients with <1% reduction in MO – non-respondersPatients with 10% reduction in MO – partial responders. Reload ×3, if responds, then T&E, if no/poor response – consider switch.Non-responders may be offered three treatment options:Switch to aflibercept.Switch to dexamethasone implantsSteroid + anti-VEGF combination (synergic combination)
Retrospective analysis of the effect of aflibercept loading dose on the retinal vessel diameters in patients with treatment-naive neovascular AMD*
Published in Cutaneous and Ocular Toxicology, 2018
Mehmet Tetikoğlu, Muhammed Mustafa Kurt, Hacı Murat Sağdık, Serdar Aktaş, Medine Aslı Yıldırım, Fatih Özcura
Anti-VEGF therapy is the first-line treatment for the management of neovascular AMD. Aflibercept is the most recently used anti-VEGF agent, and its efficacy is similar to that of bevacizumab and ranibizumab. Like bevacizumab and ranibizumab, aflibercept binds all isoforms of VEGF-A; however, it also blocks VEGF-B and placental growth factor (PlGF), which is a distinct mechanism of action when compared to bevacizumab and ranibizumab5–8,14,15. Furthermore, these anti-VEGF agents inhibit VEGF for different lengths of time. Klettner et al.16 reported that aflibercept displays a more prolonged inhibition against VEGF in tissue culture when compared to bevacizumab and ranibizumab. The long-term use of aflibercept disrupts both the physiological and pathological functions of VEGF, which could lead to undesirable effects in the retinal vasculature.
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.
Two-Year Results of a Treat and Extend Regimen with Aflibercept in Caucasian Patients with Pachychoroid Neovasculopathy
Published in Seminars in Ophthalmology, 2023
Javier Montero Hernández, Lidia Remolí Sargues, Clara Monferrer Adsuara, Verónica Castro Navarro, Catalina Navarro Palop, Enrique Cervera Taulet
Each participant was treated with a treat and extend regimen of intravitreal aflibercept (2 mg/0.05 mL), as described in previous studies. First, each study eye was treated with three monthly intravitreal injections of aflibercept in a loading phase. This was followed by a maintenance phase which the injection interval is extended by 2 weeks up to a maximum of 12 weeks, if no signs of activity were present.10,21 If there were signs of activity the injection interval is maintained or reduced by 2 weeks when the injection frequency is less than or equal to 8 weeks and more than 8 weeks, respectively. The signs of activity were newly developed subretinal fluid (SRF), no improvement of SRF, newly or persistent intraretinal fluid (IRF), CMT increase above 15%, or a diminution in BCVA of more than 5 letters. In cases with a significant increase of CMT or a reduction in BCVA of more than 5 letters, the injection interval is reduced even though the frequency of intravitreal treatment is less than or equal to 8 weeks. The number of intravitreal injections during the 24 months of follow-up was recorded in each patient.
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