Bevacizumab rescue therapy after pegaptanib provides minimal visual acuity improvement

August 1, 2007

Bevacizumab rescue therapy administered following treatment with pegaptanib (Macugen, OSI/Eyetech and Pfizer Ophthalmics) resulted in minimal improvement, said William R. Freeman, MD, at the Association for Research in Vision and Ophthalmology annual meeting. While primary bevacizumab (Avastin, Genentech) therapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) resulted in 2 to 3 ETDRS lines of improvement, which is similar to the improvement seen with ranibizumab (Lucentis, Genentech).

Key Points

Fort Lauderdale, FL-Primary bevacizumab (Avastin, Genentech) therapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) resulted in 2 to 3 ETDRS lines of improvement, which is similar to the improvement seen with ranibizumab (Lucentis, Genentech). Bevacizumab rescue therapy administered following treatment with pegaptanib (Macugen, OSI/Eyetech and Pfizer Ophthalmics), however, resulted in minimal improvement, said William R. Freeman, MD, at the Association for Research in Vision and Ophthalmology annual meeting.

"Pegaptanib has been suggested to be used in combination with ranibizumab or bevacizumab in order to reduce the numbers of treatments that patients would have to undergo over the years. Pegaptanib offers visual stabilization but not usually visual improvement," Dr. Freeman said. He is director of the Joan and Irwin Jacobs Retina Center, and professor of ophthalmology, Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, School of Medicine, La Jolla.

Considering that potential, Dr. Freeman and colleagues conducted this study to determine whether vision in eyes with CNV and initially treated with pegaptanib could be rescued with bevacizumab. The investigators compared the ETDRS visual outcomes in 38 eyes. Eighteen eyes underwent primary bevacizumab treatment (average of 3.4 consecutive injections), and 20 eyes underwent bevacizumab treatment (average of 3.6 injections) after pegaptanib therapy (average of 4.2 injections). Both groups were treated every 6 weeks with 1.25 mg of bevacizumab. The patients were followed for 6 months.

"We found that we could not rescue eyes or improve vision, even though edema, observed by optical coherence tomography (OCT), was still present in the retina, by switching treatment from pegaptanib to bevacizumab," he said.

In the primary bevacizumab group, a significant decrease in the retinal thickness was seen on OCT from before treatment to the 6-month time point. In the rescue cohort, a small amount of retinal thinning was seen, but the thinning of the retina did not correlate with an increase in the visual acuity (VA), according to Dr. Freeman.

An illustrative case was that of a patient with exudative AMD who received five injections of primary pegaptanib therapy. The VA was 10/200 before treatment with pegaptanib started and 20/450 before bevacizumab therapy. Edema and leakage were evident on fluorescein angiography. After five injections of bevacizumab, the subretinal fluid had decreased and fluorescein angiography showed mostly staining. No further improvement in the ETDRS VA was seen, however, Dr. Freeman recounted.

Direct comparison

"This is an important study in that it was a direct comparison of the 6-month data of primary bevacizumab treatment with secondary bevacizumab treatment in patients with CNV in AMD," he said, pointing out that in this study, the regimen called for injections every 6 weeks as opposed to every 4 weeks as used in some protocols. "It is possible that injections administered every 4 weeks might result in a better improvement in VA," Dr. Freeman suggested.

"Similar to the 6-month MARINA study population, which showed a seven-letter increase in VA with primary bevacizumab therapy, there was an 11-letter increase at 6 months in this study, but fewer patients had 20/40 or better VA. We believe that this study is still encouraging. We did not exclude patients with baseline VA below 20/20 or patients with subretinal gliosis, which may explain why there were fewer patients with VA of 20/40 or better," he said.

"We believe this is the first report to compare primary bevacizumab and bevacizumab rescue therapy for CNV," Dr. Freeman said. "The bevacizumab benefit is much more pronounced in primary therapy compared with secondary therapy. Changes in the neurosensory retina and the retinal pigment epithelium that seem to occur during the course of pegaptanib treatment may adversely affect the ultimate outcome in patients and do not allow rescue therapy with bevacizumab."