Session Title: Free Paper Session 14: AMD IV
Session Date/Time: Friday 08/09/2017 | 16:30-18:00
Paper Time: 17:42
Venue: Room 111
First Author: : P.Mitchell AUSTRALIA
Co Author(s): : T. Wong S. Chen E. Zhang T. Ishibashi S. Leal
Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (wAMD). It is characterised by an abnormal branching vascular network with polypoidal dilations. PCV is reported to be more common in Asians than in non-Asian populations. Prior randomised clinical trials reporting on the treatment of PCV using anti-vascular endothelial growth factor agents, alone and in combination with verteporfin photodynamic therapy (PDT), have shown inconsistent results. The aim of the PLANET study was, therefore, to evaluate the efficacy and safety of intravitreal aflibercept (IVT-AFL) monotherapy compared with IVT-AFL plus active PDT in patients with PCV.
PLANET was conducted at 62 sites (57 in Asia, 1 in Germany, 4 in Hungary). Patients aged ≥50 years with active PCV (confirmed by indocyanine green angiography [ICGA]) and a best-corrected visual acuity (BCVA) of 73–24 Early Treatment Diabetic Retinopathy Study letters in the study eye were included.
Randomised, double-masked, sham-controlled Phase 3b/4 study. All patients received 3 monthly IVT-AFL 2 mg injections. At Week 12, patients were randomised 1:1 into IVT-AFL plus sham PDT (IVT-AFL monotherapy) or IVT-AFL plus active PDT arms. Patients in both arms who did not qualify for rescue treatment received IVT-AFL 2 mg every 8 weeks (2q8); patients who qualified for rescue treatment received IVT-AFL 2q4 plus active or sham PDT, according to the randomisation arm, until visual and anatomical outcomes allowed for extension of the treatment interval. The primary efficacy endpoint was the mean change in BCVA in the study eye from baseline to Week 52. The secondary efficacy endpoint was the proportion of patients avoiding a moderate vision loss (≥15 letters) from baseline to Week 52. Exploratory endpoints included but were not limited to: (1) change in central subfield thickness ([CST] thickness of the central 1 mm of retina) over time; (2) proportion of patients with active polyps; (3) proportion of patients with complete polyp regression on ICGA; (4) area involved by polyps; and (5) proportion of patients requiring rescue therapy within the first year. The frequency and severity of ocular and nonocular adverse events (AEs) were also evaluated.
318 patients were randomised and treated. Baseline demographics/characteristics were similar in both arms. The vast majority of patients (86.8%) did not require rescue therapy; therefore, 13.2% received sham or active PDT. IVT-AFL monotherapy was noninferior to IVT-AFL plus active PDT for the primary endpoint (10.7 vs 10.8 letters; 95% CI [–2.9 to 1.6]). Patients receiving rescue showed similar outcomes (1.9 vs 4.2 letters; adjusted difference –0.5). The secondary endpoint outcome was also noninferior in the IVT-AFL monotherapy and IVT-AFL plus active PDT arms (97.5% vs 96.9%, respectively). The proportion of patients without active polyps was slightly, but not significantly, higher for IVT-AFL plus active PDT compared with IVT-AFL monotherapy at Week 52 (88.9% vs 81.7%, respectively); this was also true for the proportion of patients with complete polyp regression (44.8% vs 38.9%, respectively). The mean area of polyps showed slightly larger reduction in the IVT-AFL monotherapy arm than in the IVT-AFL plus active PDT arm (65.9% vs 60.9%). The most common ocular AEs were conjunctival haemorrhage (IVT-AFL monotherapy, 5.1%) and dry eye (IVT-AFL plus active PDT, 4.3%), and retinal haemorrhages were reported in 2.5% and 3.1% of study eyes, respectively.
In the current study, IVT-AFL monotherapy, according to the approved wAMD posology, demonstrated substantial visual acuity gains and anatomical benefits in this population of patients with PCV, including control of polyp activity. The combination of IVT-AFL with PDT did not appear to provide any additional functional benefits, and PDT therapy does not seem to be required for the vast majority of patients with PCV when treated with IVT-AFL.