• Comprehensive Ophthalmology, Retina/Vitreous

    Updated May 29

    As second year results from the Comparison of AMD Treatments Trials (CATT) were presented at ARVO this week, the focus remained on the small differences between Lucentis and Avastin.

    Daniel F. Martin, MD, study chair for CATT, said that it's "fun" to present the line graph showing the mean change in visual acuity over time between the two anti-VEGF drugs is virtually the same. "So many people come up to me and say you're so biased in favor of Avastin or you're so biased in favor of Lucentis," Dr. Martin said. "So, I think we got it right. We worked very hard to be unbiased."

    But he said the vast majority of physicians are not unbiased. They use the CATT results to justify their preferred method of treatment. When Lucentis users see the slide, they see the differences between the drugs and Avastin users see the similarities. Second year results focused on prn treatment vs. monthly treatment and found a 2.4 letter difference in favor of monthly treatment, regardless of the drug used. It also showed a 3.8 letter difference between monthly Lucentis and Avastin prn.

    When parsing CATT data, Dr. Martin urged the audience to study the means and confidence levels, and consider the metrics that matter to people, such as the number of patients seeing 20/40 or better and whether they gained or lost visual acuity. On these measures, the drugs produced the same results.

    Another metric that gets a lot of attention is one showing the retina is thinner and drier with monthly Lucentis. But the difference is just 30 µm, and it doesn't appear associated with better visual acuity. "Perhaps this difference is significant, perhaps it isn't," he said. The Lucentis monthly group also had the highest proportion of patients in which geographic atrophy developed, and as-needed Avastin had more lesion growth.

    Of all the metrics the one he and his colleagues spend more time talking about than anything else is the higher proportion of serious systemic adverse events (SAEs) that occurred with bevacizumab, 39.9 percent vs. 31.7 percent (cumulative risk ratio of 1.30).

    "We spend more time talking about this anything else and I find it fascinating to hear different theories as to why this might be," Dr. Martin said. "I don't know what it means. We looked into it exhaustively. The majority of adverse events have not been associated with Avastin complications in 10 years of clinical study. It's a bit of a puzzle."

    Among all organ systems, the greatest imbalance was in gastrointestinal disorders, 11 events with  Lucentis compared to 28 with Avastin.

    Taking a deeper dive, Dr. Martin found that these events included hernias, upper GI bleeding and diverticulitis. "It's so non-specific," he said. There were nine true cases if upper GI bleeding, two with Lucentis and seven with Avastin. But these patients also had a history of ulcer to start with or were on anticoagulants.

    While year two data failed to clarify some of the small yet controversial differences, it does show that switching to as-needed treatment after one year of monthly treatment yielded outcomes nearly equal to those obtained with as-needed treatment for the full two years.

    "Switched patients end up in the same place as prn treatment," Dr Martin said. "The take-home message is if you're treating monthly with Lucentis for the 2.4 letter difference you can't stop it. Patients must remain on continuous treatment."

    Or conversely, as noted in the following panel discussion, you can switch a monthly Lucentis patient to Avastin prn and not suffer a clinically significant decline in visual acuity.

    Two year data showed that prn patients required 10 fewer injections, 22 to 23 injections vs. 13 to 14. The endophthalmitis risk was .06 percent (11 cases/18,509 injections).

    Ultimately, physicians have to ask, "What am I buying for 10 added injections? Martin said. "Monthly might get you a little bit more. But is it worth it for 10 more injections and an increased risk of GA and the endophthalmitis risk?

    Also presented at ARVO this week were the one-year interim results of the UK's Inhibition of VEGF in Age-related Choroidal Neovascularisation (IVAN) study.

    Like CATT, IVAN was government sponsored (IVAN by the UK's National Institute of Health Research) and had similar protocols and objectives, with one difference being that all study participants in IVAN had three monthly doses of their assigned drug before continuing on a monthly regimen or switching to as-needed dosing.

    Professor Usha Chakravarthy of Queen's University Belfast, who led the research study team reported that at year one IVAN results also show that Lucentis and Avastin have similar effectiveness. Regardless of the drug received or treating monthly or as needed, there was no "clinically important difference in visual acuity between the drugs, no clinically important difference in any secondary functional outcome, no difference between drugs in regard to morphological measures, a greater decrease in serum VEGF with Avastin than Lucentis, and rare arteriothrombolic events that were more frequent with Lucentis than Avastin," she said.

    "If anything, we found a higher number of [events such as] stroke and heart failure in the Lucentis arm and we found a slight excess of other adverse events in the Avastin arm, which did not reach statistical significance in our study," said Chakravarthy. When the results from IVAN were combined with those from CATT, this difference disappeared.

    "The only place where there remains cause for concern is in hospitalizations for other events," she said. These included a range of issues, including kidney and stomach problems but, she said, they would not necessarily be a reason not to use Avastin."

    References

    2012 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting