INTREPID identifies 'best responders'

Findings from post-hoc analyses of data collected through 12 months in the INTREPID trial indicate eyes with lesions that are actively leaking, fully within the radiotherapy treatment zone, and without significant fibrosis achieve the greatest benefit. The randomized, sham-controlled, double-masked trial is investigating stereotactic radiotherapy using a proprietary device (IRay, Oraya Therapeutics, Newark, California, USA) in patients receiving anti-VEGF injections for exudative AMD.

The stereotactic radiotherapy system uses a slit-lamp style patient positioning system while delivering three X-Ray beams, which pass through the inferior sclera and overlap at the macula, coalescing over a 4 mm zone.

Patient enrolment

Patients were eligible to be enrolled in INTREPID if they had exudative AMD diagnosed within the past 3 years, had received at least three anti-VEGF injections in the prior year, were deemed to require further anti-VEGF therapy and had a lesion measuring 6 mm or less.

A total of 230 patients were randomly assigned to three groups to receive radiotherapy with a 16-Gy dose, 24-Gy dose or sham exposure. The radiotherapy was administered as a one-time treatment and patients were seen monthly thereafter. Need for further anti-VEGF injection (ranibizumab; Lucentis, Genentech) was assessed based on predefined re-treatment criteria.

For the responder analysis, eyes with actively leaking lesions were defined as those with macular volume >7.4 mm², the macular volume which represented the median volume for the study population. Within this particular subgroup, patients who received stereotactic radiotherapy had a 45% reduction in the number of anti-VEGF injections received during the first 12 months of INTREPID along with a 5-letter greater gain in best-corrected visual acuity (BCVA) compared with the sham-treated controls.

As a reference in the overall study population, stereotactic radiotherapy significantly reduced the number of anti-VEGF injections needed by 32%, and was associated with a 1.6 letter BCVA benefit, which was not statistically significant.

Eyes with both macular volume >7.4 mm² and lesion diameter <4 mm represented about one-fourth of the study population. Within this subgroup, the radiotherapy-treated eyes required 54% fewer anti-VEGF injections than the sham-treated controls and had close to a 7-letter greater gain in visual acuity.

Among eyes with lesions that were both actively leaking and that was within the treatment zone, only 20% of those receiving radiotherapy compared with 70% of controls received four or more antiVEGF injections over the course of 12 months; while 100% of control eyes received at least one additional antiVEGF injection after the mandatory baseline treatment, only 33% of the eyes in the radiation arm required anti-VEGF re-treatment, Dr Jackson noted.