Concomitant therapy of epiretinal radiation, bevacizumab for neovascular AMD promising

November 12, 2007

Concomitant delivery of focal radiotherapy and bevacizumab (Avastin, Genentech) showed promise in a small multicenter feasibility study of patients with neovascular age-related macular degeneration (AMD), said Jeffrey S. Heier, MD, a vitreoretinal specialist in private practice in Boston. Based on these findings, a phase III pivotal trial has begun. One arm will consist of brachytherapy with ranibizumab (Lucentis, Genentech) and the other will consist of ranibizumab alone as a control.

Concomitant delivery of focal radiotherapy and bevacizumab (Avastin, Genentech) showed promise in asmall multicenter feasibility study of patients with neovascular age-related macular degeneration(AMD), said Jeffrey S. Heier, MD, a vitreoretinal specialist in private practice in Boston. Based onthese findings, a phase III pivotal trial has begun. One arm will consist of brachytherapy withranibizumab (Lucentis, Genentech) and the other will consist of ranibizumab alone as acontrol.

Radiation has been considered before in the treatment of AMD, with varying degrees of success,because it has antiangiogenic, anti-inflammatory, and antifibrotic characteristics, Dr. Heiersaid.

In the preliminary study on which he reported, investigators in Boston, Mexico, and Brazil used abeta-particle emitter (Strontium-90, or Sr-90), in a NeoVista Epi-Rad90 Ophthalmic System. A dose of Sr-90 fallsoff rapidly as treatment moves away from the point source, meaning that a large dose of radiation canbe delivered with less damage to the surrounding tissue, Dr. Heier said.

The study enrolled 34 treatment naïve patients with active subfoveal lesions. They were dividedinto two groups; one received an injection of bevacizumab 10 days before radiotherapy and a secondinjection 1 month after treatment. The second group received bevacizumab at the time of theradiotherapy and 1 month after. The radiation was delivered via an epiretinal approach through avitrectomy.

Patients were followed monthly out to 12 months, with the option of re-treatment. By 12 months, whenfollow-up data were available on 27 of 34 patients, only five subjects had received additionaltherapy; four patients received one additional injection, and one patient received two.

"This means that 85% of the patients received no additional therapy," Dr. Heier said.

A rapid improvement in visual acuity occurred and was sustained over time, and patients were veryunlikely to lose vision over the course of the study. In addition, at month 12, 48% of patients hadgained at least three lines of vision. Foveal center thickness declined early in the study andcontinued to 12 months.

Safety results showed that one patient developed a retinal tear, which was easily treated. Of the 24patients who were phakic at the time of radiation therapy, 25% progressed.