CABERNET Study Did Not Meet Primary Endpoint at 2 Years

The CABERNET study evaluating epimacular brachytherapy for the treatment of wet age-related macular degeneration (AMD) did not achieve its primary visual acuity endpoint at 2 years, according to Pravin U. Dugel, MD. Dr. Dugel presented the 2-year results of the CABERNET study at the Bascom Palmer Eye Institute’s Angiogenesis, Exudation, and Degeneration 2012 meeting in Miami.

The phase 3, multicenter, prospective, randomized CABERNET study included 457 treatment-naïve patients divided into 2 arms. Patients in the treatment arm (n=302) underwent strontium-90 beta radiation with epimacular brachytherapy (NeoVista) and 2 mandatory ranibizumab (Lucentis, Genentech) injections. Patients in the control arm (n=155) received ranibizumab injections only following a modified PIER protocol, which included 3 initial monthly injections followed by injections at least once every 3 months. In the CABERNET study, patients were seen on a monthly basis, and rescue therapy was permitted at the investigators’ discretion.

The primary endpoint of CABERNET was visual acuity, specifically the percentage of patients losing fewer than 15 letters of vision. In patients treated with epimacular brachytherapy, 6 injections were required at the 2-year mark for a mean 2.5 letter loss. Patients treated with ranibizumab only required 11 injections and achieved a mean 4.4 letter gain.

In a post-study, unplanned subgroup analysis, the investigators identified 44% of patients in the epimacular brachytherapy group who required no rescue injections through the first 12 months and 1 rescue injection through the second 12 months, with a mean 3.3 letter gain, Dr. Dugel said. In a similar analysis, the investigators identified 25% of patients in the epimacular brachytherapy arm who required no rescue injections throughout the 2-year course of the study, with a mean gain of 5.7 letters.

Cataract formation occurred in 48% of patients in the epimacular brachytherapy arm, ostensibly due to the vitrectomy, according to Dr. Dugel. The difference in cardiovascular events between the 2 study groups was not clinically significant.

At the 2-year mark, there were 10 patients with suspected radiation-based retinopathy. “There are 2 important things about these patients,” Dr. Dugel said. “The first being that these 10 patients had changes that were nonproliferative and nonprogressive throughout the 2-year course of the study; the second, as a group, these patients tended to do fairly well. The mean change in visual acuity was +4.4 letters of vision. None of these patients lost significant vision, and the mean number of injections was 4.”

CABERNET demonstrated an acceptable safety profile for epimacular brachytherapy at the 2-year mark and identified a subgroup of patients that tended to respond well to the treatment. However, the study did not achieve its primary endpoint, and it is not yet known whether the subgroup of patients who benefitted from the device can be reliably and consistently identified in clinics, Dr. Dugel concluded.

“At the end of the day, I think it is important to keep this study in proper perspective,” Dr. Dugel said. “It was started in 2006 when there were few treatment alternatives. In retrospect, the CABERNET study should not have included treatment-naïve patients, but rather should have treated previously ranibizumab-treated patients only. …The CABERNET study should have placed a lot more importance on probe placement.”

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CABERNET Study Did Not Meet Primary Endpoint at 2 Years

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