Caroline Helwick

November 22, 2013

NEW ORLEANS — The latest study comparing ranibizumab (Lucentis, Genentech) and bevacizumab (Avastin, Genentech) in neovascular age-related macular degeneration shows the agents are equivalent.

The finding comes from a 1-year analysis of the head-to-head Lucentis Compared to Avastin Study (LUCAS).

"At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to an inject-and-extend protocol," reported Karina Berg, MD, from Oslo University Hospital in Norway. "There was a small but statistically significant difference in the number of required injections favoring ranibizumab," she said here at the American Academy of Ophthalmology (AAO) 2013 Annual Meeting.

The study, funded by Oslo University Hospital, was a prospective, randomized, double-blind, multicenter, noninferiority trial.

LUCAS is the first randomized, multicenter trial comparing bevacizumab and ranibizumab following an inject-and-extend protocol. With this approach, patients are treated during each visit regardless of disease activity. If there is no sign of activity, the control and treatment intervals are extended gradually; when there are signs of recurrence, the intervals are shortened. In the study, the shortest interval was 4 weeks, and the longest was 12 weeks.

"The aim of this protocol was to investigate whether such an individually developed treatment regimen is efficacious and can minimize the number of recurrences with fewer injections," Dr. Berg said.

A total of 432 patients with previously untreated choroidal neovascular membrane and edema involving the fovea were included in the study. Participants' best corrected visual acuity in the study eye was 20/25 to 20/320. Mean ETDRS letters were 61 for the ranibizumab group and 59 for the bevacizumab group. Mean retinal thickness plus subfoveal fluid thickness measurements were 369 µm and 370 µm.

At the 1-year follow-up visit, which was completed by 86% of patients, most outcomes measures were equivalent between the treatment groups, Dr. Berg reported.

Table. LUCAS Outcomes at 1 Year

Outcome Ranibizumab Bevacizumab P -Value
Visual acuity score 69.5 67.3
Change in visual acuity score from baseline 8.2 8.0 .850
Mean number of treatments 8.0 8.8 .002
Mean retinal thickness plus subfoveal fluid thickness (µm) 249 261
Mean change in thickness at fovea from baseline (µm) -120 -109 .340

 

Between groups, the difference in mean visual acuity changes at 1 year was 0.25, whereas the difference in mean thickness change at the fovea at 1 year was 10.5 µm, Dr. Berg noted.

Serious systemic events at 1 year were similar, but there was a trend for more arteriothrombotic events with ranibizumab (4.6% vs 1.4%; P = .053). Six patients in the ranibizumab group (2.8%) had a nonfatal myocardial infarction vs 0 in the bevacizumab group. Nonfatal strokes occurred in 1.4% of patients receiving ranibizumab and 0.9% receiving bevacizumab, and there was 1 vascular-related death in the bevacizumab group.

There was also a higher incidence of injury or procedural complications with ranibizumab (3.2% vs 0.5%; P = .034). The only serious ocular event was 1 case of pseudoendopthalmitis in a patient receiving bevacizumab.

Sixth Study to Confirm Equivalence

Daniel Martin, MD, from the Cole Eye Institute and the Cleveland Clinic, in Ohio, pointed out that LUCAS is the sixth study to compare ranibizumab and bevacizumab, and its results are consistent with the others, which include the CATT, IVAN, MANTA, GEFAL, and BRAMD trials.

Although the outcomes in terms of letters gained and other variables may have varied slightly among the studies, overall, the conclusion of these trials is that the agents are equivalent for visual acuity, Dr. Martin said.

"There is no question, however, that there are small differences in anatomical outcomes between the drugs," he added. "Both drugs produce immediate and dramatic improvement, but ranibizumab given monthly produces the greatest decrease in retinal thickness and residual fluid."

Dr. Martin said that the percentage of patient for whom no fluid was seen on optical coherence tomography is higher with ranibizumab, "but this is probably not clinically important," he suggested.

Dr. Martin also indicated that as-needed treatment with either drug produces excellent visual acuity results, but there is, on average, 2.4 fewer letters gained with this type of dosing vs monthly dosing.

He noted that 10% to 20% of patients need only 3 or fewer injections during the course of 1 year. "If you commit to monthly injections at the beginning, there is no opportunity to find those patients," he pointed out.

Referring to the similar safety profiles, Dr. Martin noted that there have been no differences between the 2 drugs in rates of death or myocardial infarction, stroke, or vascular death in any of the comparative trials.

The CATT trial found a trend for more arteriothrombotic events associated with treatment with bevacizumab (10.6% vs 7.5%; P = .07), as well as serious adverse events not directly related to the drug (34.5% vs 28.4%; P = .02); however, this trend was not replicated in the other trials, he pointed out.

"There is no compelling and consistent data that suggest there is a systemic safety difference between the drugs," Dr. Martin said.

Dr. Berg has served as a consultant for Bayer Healthcare Pharmaceuticals and is a member of Bayer's Norwegian Advisory Board for Eylea. Dr. Martin reports no relevant financial relationships.

American Academy of Ophthalmology (AAO) 2013 Annual Meeting. Presented November 15, 2013.

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