CATT at 2 Years: The Facts

Charles C. Wykoff, MD, PhD; David M. Brown, MD

Disclosures

August 13, 2012

In This Article

Safety of Bevacizumab vs Ranibizumab

Phase 3 randomized, controlled trials leading to FDA approval of pharmaceuticals typically evaluate both efficacy and safety. For example, MARINA, ANCHOR, and PIER together analyzed more than 1300 patients and found no statistically significant safety issues.[6,7] Because bevacizumab is not FDA-approved for treatment of neovascular AMD, rigorous prospective data on ocular-specific dosing (typically 1.25 mg in 50 µL, given intravitreally) are not available, and the best available data to date are from CATT and IVAN, which included 502 and 296 patients respectively (a total of 798 patients treated with bevacizumab).[10,17]

Phase 1 and 2 trials of bevacizumab identified hemorrhage, thromboembolism, proteinuria, and hypertension as possible adverse events.[18] In a phase 3 trial of bevacizumab added to a chemotherapy regimen for the treatment of metastatic colorectal cancer, bevacizumab was given intravenously at 5 mg/kg every 2 weeks,[9] a dose several hundred times higher than that typically administered in the treatment of neovascular AMD. In that trial, patients were sicker and more likely to have other medical events than the patients with neovascular AMD enrolled in CATT and IVAN. Nevertheless, the rate of grade 3 or 4 adverse events was 10% higher with bevacizumab treatment than without (84.9% vs 74%), a difference that was primarily attributed to an increase in the incidence of hypertension (22.4% vs 8.3%). Therefore, trials evaluating VEGF inhibitors have closely considered the rates of vascular events, such as arterial thrombotic events (vascular death, nonfatal myocardial infarction, and stroke).

Two-year data from CATT found that the arterial thrombotic event rates were similar between the 2 drugs (P = .89), but the proportion of patients with 1 or more serious systemic adverse event was significantly greater with bevacizumab than with ranibizumab: 39.9% vs 31.7% (P = .004). In comparison, in the interim 1-year analysis in IVAN, ranibizumab treatment was associated with a significantly higher rate of arterial thrombotic events than was bevacizumab treatment (2.9% vs 0.7%; P = .03). IVAN reported more serious systemic adverse events in bevacizumab-treated patients (12.5%) than in ranibizumab-treated patients (9.6%), a nonsignificant difference (P = .25).

Cost Consideration

In both CATT and IVAN, the most dramatic difference between the 2 drugs was cost.[10,16,17]

In CATT, the average drug cost was higher for ranibizumab ($25,000-$45,000) than bevacizumab ($700-$1200), depending on the regimen prescribed.

In IVAN, ranibizumab treatment cost an average of £2905-£9656, whereas bevacizumab treatment cost an average of £1509-£1654, depending on the prescribed regimen (P < .001).

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