INTREPID Trial: Radiotherapy Safe for Macular Degeneration

Damian McNamara

September 27, 2013

HAMBURG, Germany — Stereotactic radiotherapy, which significantly reduced the need for anti-vascular endothelial growth-factor (VEGF) injections in patients with age-related macular degeneration at 12 months, appears to be safe, according to 2-year data from the INTREPID trial.

Investigators found "no particular pattern of adverse events in the radiation or control groups. Although some patients had microvascular changes, these seldom affected vision," said lead investigator Timothy Jackson, PhD, FRCOphth, a consultant ophthalmic surgeon at King's College Hospital in London, United Kingdom.

Dr. Jackson presented the findings here at the 13th EURETINA Congress.

In the double-masked, sham-controlled study, investigators from 21 sites in Europe evaluated participants with neovascular age-related macular degeneration.

Each patient received a 0.5 mg intravitreal injection of ranibizumab (Lucentis, Genentech, Novartis) at baseline and monthly injections as required for 12 months. After that, they returned to usual care.

At baseline, 226 participants were randomized to receive radiotherapy — 16 or 24 Gy — with the IRay stereotactic radiation system (Oraya Therapeutics) or sham radiotherapy.

 
I think most patients would potentially trade small microvascular abnormalities outside the fovea to get fewer injections.
 

The only clinically significant or serious adverse event related to treatment was radiotherapy-related retinopathy, which was reported by 1 patient in the 24 Gy group.

Independent reviewers assessed fundus photographs and fluorescein angiograms obtained at baseline, month 12, and month 24, and additional color images obtained at months 6 and 18. Any suspicious microvascular abnormalities potentially associated with radiotherapy triggered referral to experts for additional evaluation.

At 24 months, some subtle microvascular abnormalities were observed. "More than half were outside the 4 mm treatment zone, were generally scattered, and would not be expected to affect the vision," Dr. Jackson reported.

In fact, visual acuity did not differ significantly in the treatment and control groups.

The risk/benefit ratio appears to favor stereotactic radiotherapy. "I think most patients would potentially trade small microvascular abnormalities outside the fovea to get fewer injections," Dr. Jackson noted.

Table. Patients With Microvascular Abnormalities at 24 Months

Radiotherapy Group n %
16 Gy (n = 74) 13 18
24 Gy (n = 73) 16 22
Sham (n = 79) 16 22

 

The best candidates for this treatment are probably those who present with significant fluid from active, proliferative disease and/or with lesions in the 4 mm treatment zone, Dr. Jackson explained.

Although treatment was associated with a significant 25% reduction in the number of anti-VEGF injections over 2 years, there appears to be room for improvement. "With appropriate case selection, injections were reduced by 45% and there was a trend for better visual acuity."

"We also saw a 4-letter difference in vision change, which was not significantly different, but radiotherapy-treated patients had a trend to better vision at 24 months," Dr. Jackson reported.

"These results are really promising," said Wilfred Ngwa, PhD, from the Department of Radiation Oncology at Brigham and Women's Hospital and Harvard Medical School in Boston, who was asked by Medscape Medical News to comment on the findings.

"There is a growing consensus from other experts who have recently reviewed this approach that stereotactic radiotherapy — for example with the Oraya system — has great potential. However, it will be necessary to see the data beyond 2 years, especially because some toxicity effects can be late," he pointed out.

"That said, there may be ways to reduce the issue of toxicity," Dr. Ngwa said. "We are currently developing a possible approach at Harvard Medical School to enhance radiotherapy for neovascular age-related macular degeneration" (Phys Med Biol. 2012;57:6371-6380).

Session moderator Jean-Jacques De Laey, MD, said he agrees that safety monitoring beyond 2 years might be warranted.

"We plan to continue study out to 3 years," Dr. Jackson said. "Safety is something we will have to always pay attention to."

This study was sponsored by Oraya. Dr. Jackson reports that his institution, as one of the INTREPID study sites, received research funding from Oraya, and that he received conference support from Oraya. Dr. Ngwa and De Laey have disclosed no relevant financial relationships.

13th EURETINA Congress. Presented September 26, 2013.

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