番茄社区

Positive 3-year results from the phase III PHOTON study were presented at the recent American Academy of Ophthalmology (AAO) meeting, demonstrating that patients with diabetic macular edema (DME) achieved sustained vision improvements with extended dosing intervals and no new safety signals with aflibercept 8 mg (Eylea HD).

番茄社区 brought together three expert leaders in the field: Moderator Peter K. Kaiser, MD, of the Cleveland Clinic, is joined by Yasha S. Modi, MD, of New York University Langone Health in New York City, and Arshad M. Khanani, MD, of the University of Nevada in Reno, for a virtual roundtable discussion. This third of four exclusive episodes focuses on the implications of the PHOTON study's 3-year data.

Click here to watch the other videos from this AAO roundtable series.

Following is a transcript of their remarks:

Kaiser: Arshad, one of the other late breakers that Dr. Diana Do presented was the 3-year results of the PHOTON study. Maybe you can tell our viewers, first of all, what is the PHOTON study and then what were some of the findings in year 3?

Khanani: So, absolutely, Peter. So Diana, as usual, gave an excellent talk on the 3-year results of the PHOTON study, which is obviously the pivotal study that led to the approval of aflibercept 8 mg for the treatment of diabetic macular edema. In this study, obviously patients received three loading doses of aflibercept 8 mg, followed by disease activity criteria and interval adjustments based on those criteria. And what we have seen is durability that's much better than what we saw with aflibercept 2 mg. Of course, given that aflibercept 2 mg was given on a fixed regimen.

So in this study, patients had the opportunity to extend their interval to 12, 16, and 20 weeks. And the data that was presented by Diana Do was very impressive that in the third year, 88% of patients could go 12 weeks or longer. And then when you look at 20-weekers, it was 48% of patients could go 20 weeks or longer in terms of treatment interval, really highlighting the benefit of durability that we have seen with aflibercept 8 mg.

So I think, and of course safety is important. There is no new safety signal in this 3-year dataset. So I think it's something that is very relevant for practicing physicians that in the past we were very obviously nervous about extending patients past 8 or 12 weeks. Now, of course, these diabetic macular edema, and the question becomes, obviously, is when do you stop treatment or not? So overall, it's a very positive dataset that was presented.

Kaiser: Yeah, I totally agree. And Yasha, it begs the question, when you're out at 20, and in the case of PHOTON even went out to 24-week intervals, so twice a year. At what point do you actually switch from say, a treat-and-extend paradigm or to say a PRN [pro re nata, or "as-needed"] paradigm?

Modi: Yeah, I mean, I think that's a great question. And I certainly think for those patients who get out to 20 weeks, especially 24 weeks, you start to wonder, can you switch these patients to a PRN basis? And so for me, even before I saw this data, I think when patients in my clinic get out to about 16 weeks, that's the window when I tend to sort of say, "Hey, well, let's go back to a PRN window." And I'm oftentimes surprised as to how many patients go injection free for a couple of years after that.

Kaiser: Yeah, I totally agree.

Khanani: So I have a quick question for Yasha, Peter. So Yasha, what if somebody had PDR [proliferative diabetic retinopathy]and DME and then you now are at 4 months, how do you manage? Does this dataset help you at all, of course, it's addressing the DME piece? What do you do with those patients? Do you PRP [panretinal photocoagulation] them, continue anti-VEGF, or...

Modi: Yeah, that's a great question. I think oftentimes we sort of have a conversation about binarization of the treatment of PDR or even very severe NPDR [non-proliferative diabetic retinopathy] into anti-VEGF injections versus PRP. But there was a study that really didn't get a lot of press called the , and it looked at basically PRP plus anti-VEGF therapy versus PRP alone. So it wasn't just an anti-VEGF arm, and it showed that with the combination approach, neovascularization rates were drastically reduced.

So to me, anybody with PDR is going to get PRP. We know from the Protocol S 5-year study, even when you give anti-VEGF therapy, their visual function scores go down because they have progressive nonperfusion, even in the setting of anti-VEGF therapy. And so I think the risk of not treating them to me is just too high. And studies have shown that up to half of patients at 5 years will be lost to follow-up for greater than 6 months.

So that's a lot of loss to follow up in patients who are diabetics. And there has to be a critical level of negligence to get to PDR in the first place, in order for you to have poor glycemic control. So for me, I really think PRP needs to be a mainstay of treatment and anti-VEGF is a critical element to help achieve the best outcome.

Kaiser: Yeah, and a lot of it also has to do with where you live. So in Cleveland, as you said, correctly, Yasha, the patients don't take care of themselves and they may never show up again. So if I can get PRP in, I know at least I've prevented them from going blind. I can't count on them for coming back for even every-24-week injections of aflibercept 8 mg. But then again, you're in New York, you have patients who want to probably come in weekly because they're so neurotic. And then in Reno, maybe things are a little different, but you're probably closer to Cleveland than New York in terms of the patient.

Khanani: Correct. That's why I practice here.

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