Avastin/Lucentis Update 42: One-Year Results of Controlled Comparison Study Published
Posted Oct 04 2010 2:08pm
Last October, I came across the six-month results of one of the first blinded, double-masked comparison studies run between Avastin and Lucentis, sort of a mini-CATT Study. This study was done by researchers at the Boston University School of Medicine in cooperation with the VA Boston, and was published in the American Journal of Ophthalmology. I published their news release describing the study and the six-month results as Avastin/Lucentis Update 29 .
This weekend, the same group announced the one-year results of this study, this time published in Eye, a peer-reviewed publication of The Royal College of Ophthalmologists in the UK.
This study, although done with a minuscule sample size compared to the CATT Study (twenty two patients enrolled, compared with 1200 in the CATT Study), is probably an indicator of what to expect when the results of the CATT Study are released, some time early next year.
Researchers from Boston University School of Medicine (BUSM) and the VA Boston Healthcare System have conducted a study that failed to show a difference in efficacy between Bevacizumab (Avastin) and Ranibizumab (Lucentis) for the treatment of age-related macular degeneration (AMD). The study, which appears currently on-line in Eye, is believed to be the first study to describe one-year outcomes of a prospective, double-masked, randomized clinical trial directly comparing bevacizumab to ranibizuamab. Last October, these same researchers published early, six month outcomes of the same study, which also failed to show a difference in efficacy between these two drugs for treating AMD.
AMD is the leading cause of blindness over the age of 50 in developed Western countries. It presents in two forms, exudative (wet) or nonexudative (dry). Wet AMD is often more visually devastating with a higher risk of blindness. The gold standard of treatment for wet AMD is ranibizumab (Lucentis, Genentech Inc.), which was FDA approved as an eye injection in 2006. Bevacizumab (Avastin, Genentech Inc.) was FDA approved for the treatment of colorectal cancer in 2004, but has also been used worldwide in an off-label fashion as an eye injection for the treatment of wet AMD. Lucenitis costs approximately $2000.00 per injection, while Avastin costs approximately $50.00 per injection. While both drugs have shown independently to be effective in treating wet AMD, it was uncertain if both drugs were equally efficacious or if either one was better.
In this study, patients were enrolled in a 2:1 ratio to receive either the Avastin or Lucentis. Patients were given eye injections of Avastin or Lucentis every month for the first three months, followed by monthly examination and testing. They received further injections on an as needed basis for one year.
Fifteen patients received Avastin and seven patients received Lucentis. There was no significant difference in visual acuity and anatomic outcomes between the two groups. Both groups had an average improvement in vision of 1.5 lines on the vision testing chart, and only one patient (who was in the Lucentis group) lost a significant amount of vision (three lines or more). In addition, patients in the Avastin group underwent an average of eight injections over one year, while patients in the Lucentis group underwent an average of four injections.
"With the exception that total injections given to subjects over one year were significantly different between the two treatment arms, visual and anatomic outcomes at one year failed to show a significant difference between both groups," said lead author and Principal Investigator Manju Subramanian, MD, an assistant professor in Ophthalmology at BUSM. According to the authors, further studies with larger sample sizes are warranted.
This study is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System, Jamaica Plain, Mass., USA. The VA Boston funded the cost of medications for this study.
To report 1-year visual and anatomic outcomes of a prospective, double-masked randomised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration (AMD).
Patients who met inclusion criteria were randomised 2:1 to bevacizumab or ranibizumab. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity was taken on an Early Treatment Diabetic Retinopathy Study chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by an optical coherence tomography-guided, variable-dosing treatment schedule. Main outcomes measured included visual acuity, foveal thickness, and total number of injections over the 1-year treatment period.
In total, 15 patients received bevacizumab and 7 patients received ranibizumab. The average pre-operative visual acuity was 34.9 letters in the bevacizumab group, and 32.7 letters in the ranibizumab group. At 1-year follow-up, mean vision was 42.5 letters in the bevacizumab group, and 39.0 letters in the ranibizumab group. Two-tailed t-test failed to showed statistical significance between the two groups (P=0.5). Patients in the bevacizumab group underwent an average of eight injections, whereas patients in the ranibizumab group underwent a mean of four injections (P=0.001).
The 1-year outcomes of a prospective, double-masked, randomised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD. Total injections given over the treatment period were significantly different between the two groups. Further studies with larger sample sizes are warranted.
Some of the accompanying graphics are presented below:
Table 1. Patient Demographics Distribution
Table 3 Summary of Visual Acuities and Anatomic Outcomes
Figure 1 Visual Acuities
Figure 2 Central Macular Thickness
It is interesting to note that although no difference was found in visual outcomes between Avastin and Lucentis, fewer injections of Lucentis were required to maintain the visual outcomes. The authors tried to explain this as follows “Patients in the bevacizumab (Avastin) group underwent statistically significant more injections than those in the ranibizumab (Lucentis) group (p=0.001). The reason for this is unclear and difficult to interpret. As a larger molecule with a longer half-life, one would intuitively expect patients receiving bevacizumab to undergo fewer injections. One possible reason for this may be a tachyphylactic response.” (A rapidly decreasing response to multiple doses of a drug.)
“Results from the Pan-American Collaborative Retina Study found, when comparing 2 doses of bevacizumab (1.25mg vs 2.5mg) that patients receiving the higher dose underwent more injections (Arevalo JF, Sanchez JG, Wu L, et al. Comparison of 2 doses of primary intravitreal bevacizumab for subfoveal CNV in AMD at 24 months: Results from the Pan-American Collaborative Retina Study Group. Association for Research in Vision and Ophthalmology, May 3, 2010).”
“An alternative possibility is that patients in the ranibizumab group had a more robust and immediate response during the first 3 months than those in the bevacizumab group, (see Figure 2), and as OCT findings were the primary guide for re-treatment, the early and more dramatic change in foveal thickness in this treatment arm may have contributed to fewer injections over time.”
It will be interesting to see how this small study correlates to the larger study(s) as the CATT Study and other comparative studies – undertaken in several countries around the world – are released over the next year or so.