showed that 54.8 percent of patients had complete regression of polypoidal lesions at month 6; and by month 12 the number increased to 72.5 percent. The VAULT study is another example of aflibercept monotherapy, where patients with PCV gained an average of 9 letters at month 12 and showed an improvement in their central macular thickness. In the same study, 67 percent of patients had polyp regression after 12 months. Dr. Kim also highlighted results from first year of the PLANET study which looked at the safety and efficacy of intravitreal aflibercept (IVT-AFL) monotherapy for treatment of PCV. In this study, all patients received a three-loading dose of IVT-AFL. At three months, participants were randomized into two groups: one with an active rescue PDT arm, the other with a sham arm. At 52 weeks, there was an option for treat-and-extend (T&E). In the first year, investigators found that patients gained an average of 10 letters and only 15 percent of participants required rescue PDT. At the end of year one, they concluded that IVT-AFL monotherapy was noninferior to IVT-AFL plus PDT. In addition, real world studies are corroborating this clinical trial data. In two different post-marketing studies (PMS) in Japan and Korea, patients with PCV treated with IVT-AFL achieved vision gains similar to the PLANET study.
Exploring PLANET’s year two results Adding to the conversation on aflibercept monotherapy was Dr. Tien Yin Wong from Singapore National Eye Centre (SNEC), who discussed year two results from the PLANET study. “The idea behind the PLANET study was to show the non-inferior qualities of monotherapy,” explained Dr. Wong. “So, if indeed it [PCV] is what we’re now thinking, that it’s a type 1 CNV AMD, what would you expect PLANET to show over two years?” Dr. Wong says that from 52 to 96 weeks, patients maintained a nine to 10 letter gain – and this is a good outcome
for patients. In addition, 94 percent of study participants avoided a loss of vision and more than 80 percent had a dry retina at 52 weeks and up to 96 weeks. “Basically, this fits with our clinical experience of treating PCV like nAMD,” said continued Dr. Wong.
Polyp activity versus regression Another outcome of PLANET assessed polyp regression. At 96 weeks, about 30 percent of patients had complete polyp regression – suggesting that two-thirds of patient had some sort of polyp. But are they active polyps? Not necessarily, in fact more than 80 percent did not have active polyps. This is where Dr. Wong makes an important distinction between polyp activity and regression. “Sometimes, polyps are seen (on ICGA) without any activity – meaning there’s no fluid or impact on function. You may not need to treat if those polyps have not regressed, and if there is no activity” he said. “An active polyp is not the same of having one that’s just still there.” Dr. Wong says that longer term data is needed to determine if aflibercept monotherapy is sufficient for complete polyp regression, noting that patients who received rescue PDT did not have any additional polyp regression.
So, what about PDT? Studies, like those mentioned above, have shown that IVT-AFL monotherapy has several benefits over PDT combination therapy. It provides meaningful outcomes in diverse disease subtypes; it’s a simple regimen with no need to purchase specialized equipment; and it avoids the potential long-term side effects associated with PDT. So, with that said, what role should PDT play in the future? Dr. Kim warns against mandating PDT at baseline – this could result in overtreatment for many patients, noting that at week 12 of the PLANET study, only 6 percent of patients qualified for rescue PDT treatment. “Anti-VEGF monotherapy is a simple regimen, and there is no need
to access special equipment,” said Dr. Kim, explaining that PDT requires more preparation, is more time-consuming to perform, is costlier to acquire and maintain, and requires specific training. There are also side-effects associated with long-term use of PDT. “Treating these patients repeatedly with PDT could result in the occlusion of the choriocapillaris which may lead to RPE atrophy,” said Dr. Kim. He also mentioned other studies concerning long-term PDT use – one of which found a 64 percent recurrence of polypoidal lesions and an abnormal branching vascular network (BVN) in all patients. Thus, the PLANET study is setting the stage to enable PDT to be reserved as a rescue treatment. Dr. Kim notes that this combination therapy (IVT-AFL plus rescue PDT) could be considered in the following cases: if there’s a loss, no change or insufficient VA gains; if persistent fluid is showing on OCT; or if active polyps are observed on ICGA. Dr. Wong also mentions that PDT does not help non-responders: “We know that in all AMD cases, there is a group that will not respond . . . the fluid will be there and it will be difficult to improve their vision.” And he says that patients who don’t respond to monotherapy likely won’t respond to PDT either: “The small group that’s not responsive – even if you want to do PDT, it doesn’t help that much anyway. This group just doesn’t respond.” Overall, results from PLANET (and other studies) have shown that IVT-AFL is non-inferior to combination PDT therapy. In addition, the average number of injections was reduced in the second year of PLANET (where there was a treat-and-extend option), from about 8 injections to 4.6 – which can help ease the treatment burden on both patients and doctors. And, indeed, these results certainly pave the way for improvement in diagnosis and treatment for patients with PCV. Editor’s Note: The APVRS 2018 Congress was held in Seoul Korea, on December 14-16, 2018. Reporting for this story also took place at APVRS 2018.
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