UPFRONT

CATT out of the Bag

Jason S. Slakter, MD

Well, after months of anticipation, and an ongoing CATT and mouse game of trying to get an early answer, the results are finally here. To almost no one's surprise, after one year of monthly dosing, bevacizumab was shown to be noninferior to ranibizumab when administered to patients enrolled in this clinical trial. The PRN arms performed similarly as well. From a safety point of view, the results were equally as expected, with no significant difference in adverse events reported for either drug used in either treatment protocol, although there were some imbalances in serious systemic adverse events noted.

So now, after all of the excitement and discussion, does this really change anything? It is estimated that 60% of retina specialists in the United States already use bevacizumab as their first-line treatment for CNV secondary to AMD. For those physicians who have been using ranibizumab, the fact that bevacizumab was noninferior in the context of the study will not necessarily change the way they practice. In fact, just because the data show that the mean outcomes were similar among the patients enrolled in the trial does not mean that for a particular individual the two drugs are equal. We should remain open to the possibility that, for an individual patient, these drugs may behave differently, and adjustments in therapy may be required depending upon an individual's response to treatment.

There is much more to be learned from CATT, not the least of which is the ability of a determined group of investigators (led by the indomitable Dan Martin) to succeed in answering critical clinical questions in the context of a well-designed and -conducted study, despite the lack of support of the pharmaceutical company involved in the production of the drugs under investigation. It was only through the creative and diligent work of Dan and his team that this trial was even possible, and to everyone involved in the organization and execution of this study we owe a debt of gratitude.

I also look forward to reviewing the data with an eye toward a more in-depth analysis of the trial. In particular, it will be crucial to assess the two-year outcomes given the differences in the anatomic effects of the two drugs, as well as the differences in serious adverse events seen in the first year of treatment. Furthermore, I am very interested to see an analysis of those patients who seem to be “poor responders” to either drug and to understand better where anti-VEGF therapy itself may have shortcomings.

The elephant in the room, of course, is the question of what we do with the next set of drugs when they come along. Within just a few months, VEGF Trap-Eye will likely become available, and early indications suggest that this drug may not be just a copy-CATT, but instead have some advantages over ranibizumab with regard to efficacy and durability. Therefore, do we need a CATT 2? Will this CATT have nine lives? Or, instead, are we simply going to apply our best judgment to selecting the appropriate anti-VEGF therapy for our patients? For myself, I plan to keep an open mind. After all, there is more than one way to skin a CATT.