Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study: A Randomized Clinical Trial

Abstract

Importance: Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed.

Objective: To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT).

Design, setting, and participants: This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent).

Interventions: Participants received 2 mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a "rescue" of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks.

Main outcomes and measures: Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95% CI of the difference entirely above -5 letters).

Results: Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95% CI, -2.9 to 1.6; P = .55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (-137.7 [IAI monotherapy] vs -143.5 μm [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]).

Conclusions and relevance: Improvement in visual and/or functional outcomes was achieved in more than 85% of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15% met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined.

Trial registration: ClinicalTrials.gov Identifier: NCT02120950.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lee reports receiving personal fees and nonfinancial support from Bayer during the conduct of the study and personal fees from Bayer, Novartis, Allergan, and Santen outside the submitted work. Dr Iida reports receiving personal fees from Bayer during the conduct of the study; grants and personal fees from Alcon, AMO Japan, Bayer, Novartis, Otsuka Pharmaceutical, Santen Pharmaceutical, Senju Pharmaceutical, and Wakamoto Pharmaceutical; grants from Canon, Hoya, Kowa, Nidek, and Pfizer; and personal fees from Bayer and Chugai Pharmaceutical outside the submitted work. Prof Ogura reports receiving personal fees from Bayer during the conduct of the study and personal fees from Bayer, Alcon, Bausch and Lomb, Janssen Pharma, Kissei Pharma, Kowa, Novartis, Santen, Sanwa Kagaku, Senju, Topcon, and Wakamoto outside the submitted work. Dr Chen reports receiving personal fees and nonfinancial support from Bayer, Novartis, and Allergan and personal fees from Medical Integrating System during the conduct of the study. Dr Wong reports receiving consultancy fees and payments for lectures from Abbott, Allergan, Bayer, and Novartis outside the submitted work. Dr Mitchell reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. Dr Cheung reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. Drs Zhang and Leal are employees of Bayer Pharmaceuticals. Dr Ishibashi reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work.

Figures

Figure 1.. Consolidated Standards of Reporting Trial Diagram of Study Participant Disposition

IAI indicates intravitreal aflibercept injection; PDT, photodynamic therapy.

Figure 2.. Functional and Anatomic Outcomes

A, Change in best-corrected visual acuity (BCVA) from baseline to week 52 (last observation carried forward [full analysis set]). B, Change in central subfield thickness (CST) from baseline to week 52. Last observation carried forward (fullanalysis set [FAS]). C, Proportion of participants with absence of fluid detected on optical coherence tomography (OCT) over 52 weeks (observed cases [safety analysis set]). ETDRS indicates Early Treatment Diabetic Retinopathy Study; IAI, intravitreal aflibercept; PDT, photodynamic therapy.