Results of the LEAVO trial presented at AAO 2019 reveal a low level of confidence among investigators for recommending bevacizumab treatment as equivalent to ranibizumab and aflibercept at 100 weeks.
Philip Hykin, MBBS
Results of the LEAVO study are offering ophthalmologists greater insight into the cost-effectiveness and efficacy of some of the most popular anti-VEGF treatments for patients with macular edema due to central retinal vein occlusion.
Based on data from the phase 3 trial, which compared aflibercept, bevacizumab, and ranibizumab, investigators concluded they had little confidence for recommending bevacizumab treatment as equivalent to either of the other anti-VEGF therapies examined.
“Bevacizumab may or may not be worse than ranibizumab or aflibercept. For patients managed as in this study, we would have low confidence in recommending bevacizumab treatment as equivalent to ranibizumab and aflibercept over 100 weeks,” said Philip Hykin, MBBS, a consultant in ophthalmology at London Medical.
Presented at the American Academy of Ophthalmology (AAO) 2019 Annual Meeting in San Francisco, LEAVO was a phase 3, multicenter, double-masked, randomized, controlled, non-inferiority trial examining the clinical and cost effectiveness of the 3 anti-VEGF treatments over the course of 2 years. A total of 463 patients were included in the study and they were randomized in a 1:1:1 ratio.
The primary endpoint measure of the study was change in BCVA ETDRS letter score from baseline to 100 weeks in the study eye. Secondary endpoints included proportion of patients gaining 10 or more and 15 or more letters, the proportion of patients losing less than 15 or 30 more letters at week 100, change in OCT central subfield thickness from baseline to week 52 and 100 weeks, the number of injections performed in the study eye at 100 weeks, and local and systemic side effects.
A total of 155 patients were randomized to receive ranibizumab, 154 received aflibercept, and 154 received bevacizumab. Baseline characteristics were similar across all 3 arms of the study. At 100 weeks, the mean gain in BCVA with ranibizumab was 12.5 compared to 15.1 with aflibercept and 9.8 with bevacizumab.
In the intent-to-treat analysis, investigators found bevacizumab was not non-inferior to ranibizumab(95% CI: -1.73 (-6.12, 2.67)). Additionally, investigators noted aflibercept was non-inferior to ranibizumab, but it was not superior (95% CI: 2.23 (-2.17, 6.13)). Additionally, investigators noted less injections at week 100 among those who received aflibercept(9.8) compared to bevacizumab(11.5) and ranibizumab(11.8). Based on results, investigators concluded bevacizumab was not non-inferior to ranibizumab at 100 weeks, aflibercept was non-inferior to ranibziumab but not superior, and bevacizumab was not non-inferior to aflibercept at 52 weeks.
This study, “A Multicentre Phase 3 Double-Masked Randomised Controlled Non-Inferiority Trial Comparing the Clinical and Cost Effectiveness of Lucentis vs. Eylea vs. Avastin In Macula Oedema Due To Central Retinal Vein Occlusion (LEAVO),” was presented at AAO 2019.