NVI-111 trial analysis: Combination treatment found effective for CNV

November 1, 2009

Combination epimacular brachytherapy and anti-vascular endothelial growth factor therapy may help achieve and maintain optimal visual acuity outcomes over the long term in patients with neovascular age-related macular degeneration.

After 2 years of follow-up in 34 patients treated with strontium 90 beta ionizing radiation with concomitant bevacizumab, 80% of patients who had cataract surgery before the study maintained vision and 30% gained significant vision. When compared with patients who had their natural lens, 65% of patients maintained vision and 20% gained significant vision, suggesting an effect of cataract formation on long-term visual acuity outcomes.

Another important study finding is that about three-quarters of the patients required only two injections (mean, 2.4 injections) of bevacizumab during the course of the study, he said.

The trial, which took place in two centers in Brazil and one center in Mexico from June 2006 to April 2007, included 34 patients (mean age, 72 years) with predominantly classic, minimally classic, or occult (with no classic) CNV. They received one dose of 24-Gy epimacular brachytherapy via vitrectomy and two 1.25-mg injections of bevacizumab 1 month apart.

The patients were given one injection of bevacizumab a mean of 10 ± 4 days before surgery or immediately after the surgery; the second injection was administered 1 month after surgery.

Additional injections of bevacizumab during the 3-year follow-up period were administered at the surgeons' discretion.

The treatment was evaluated for safety and efficacy. Patients were evaluated by slit-lamp examination, indirect ophthalmoscopy, fluorescein angiography, and optical coherence tomography to determine the incidence and severity of any ocular adverse events, according to Dr. Dugel.

Reported adverse events

The following adverse events associated with treatment were reported, and all of them were associated with vitrectomy rather than the epimacular brachytherapy. The adverse events included cataract development (>2 grade increase based on the Lens Opacities Classification System, version II) compared with baseline in 12 (50%) of 24 phakic patients, and subretinal fibrosis in two (5.8%) of 34 patients. An epiretinal membrane, a retinal tear, and a subretinal hemorrhage each developed in one (2.9%) of the 34 patients.

Importantly, no radiation retinopathy was observed at 24 months after treatment, he said.

Advantages

An important advantage of this novel treatment is that the 2-year results did not show toxicity from long-term radiation, and no effects from radiation were seen in patients, many of whom were followed for as long as 3 years, according to Dr. Dugel.

"This therapy has the potential to decrease the burden of treatment for both patients and physicians, not to mention the overall financial burden for health-care systems around the world," he said.

The dose delivered to the retina is directly delivered to the CNV lesion, thereby minimizing damage to collateral tissues. The maximum depth and diameter of the delivered energy are 3 mm in depth and 5.4 mm in diameter, respectively, according to Dr. Dugel.

"The potential of this treatment is enormous," he said. "I believe that epimacular brachytherapy may be used in combination with the current standard of care to make this treatment more effective by offering a broad spectrum of action. In addition, epimacular brachytherapy may also improve the quality of life for our patients by relieving them from having to receive monthly intraocular injections. The potential impact of epimacular brachytherapy for patients, physicians, and the entire health-care system is prodigious."