Intravitreal aflibercept compared with laser photocoagulation for infants with retinopathy of prematurity: A FIREFLEYE subgroup analysis

Abstract

Purpose : FIREFLEYE was the first randomized, controlled, multicenter, international Phase 3 trial of patients with treatment requiring retinopathy of prematurity (ROP) that compared the treatment effects of intravitreal aflibercept (IVT-AFL) to laser. It was also the first ROP study to include Zone II Stage 2+ eyes, permitting unilateral treatment, and using a low injection volume of only 0.01 mL IVT-AFL per eye (20% of the approved adult dose and injection volume). Previously reported primary results demonstrated treatment success (absence of active ROP and unfavorable structural outcomes at Week [W] 24 based on investigator assessment) with IVT-AFL to be numerically higher compared with laser (85.5% versus 82.1%). This was considered clinically relevant, while non-inferiority could not be formally shown. Here, we report a post hoc analysis of the primary endpoint for subgroups stratified by gestational age and weight at treatment.

Methods : FIREFLEYE (NCT04004208) enrolled infants born at gestational age ≤32 weeks or birth weight ≤1500 g, weighing ≥800g at time of first treatment, who had ROP Zone I Stage 1+, 2+, 3+/-; Zone II Stage 2+, 3+; or aggressive posterior ROP in at least one eye. Infants were randomized 2:1 to receive IVT-AFL 0.4 mg or laser photocoagulation. Re-treatment and/or rescue treatment (IVT-AFL rescue for the laser group, laser rescue for the IVT-AFL group) was administered if any of the prespecified criteria were met.

Results : Treatment success in the subgroup of infants with low weight <1500 g at first treatment (n=24) was 87.3% in the IVT-AFL group (n=14) compared to 66.0% in the laser group (n=10). In infants with gestational age <27 weeks (n=77), treatment success was 85.7% for IVT-AFL (n=49) versus 80.0% for laser (n=28). Results for additional subgroups, e.g., infants with Zone II Stage 2+ ROP and infants treated unilaterally, will also be presented.

Conclusions : Overall, FIREFLEYE data consistently show that treatment of ROP patients with IVT-AFL 0.4 mg is clinically efficacious and safe. Subgroup analyses suggest that IVT-AFL may be a sensible alternative to laser treatment particularly for infants born at less than 27 weeks of gestational age and/or weighing less than 1.5 kg at time of first treatment.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.