Abstract
Purpose :
The programmed death-1 (PD1) pathway inhibitors, including agents targeting PD1 and programmed death-ligand 1 (PDL1) have been approved for treatment in several malignancies and are being studied in over 3000 clinical trials. The drugs are known to cause unique immune-related adverse effects due to nonspecific immunologic activation. Little is known about PD1/PDL1 inhibitor-associated adverse events in the eye. This is the first analysis of serious ocular adverse events (AEs) submitted to the National Cancer Institute’s Cancer Therapy Evaluation Program (CTEP), the largest public sponsor of oncology clinical trials globally.
Methods :
Adverse events from studies using at least 1 PD1/PDL1 inhibitor in the CTEP network were assessed. CTEP’s database of serious adverse events was queried for reports up to October 9th, 2019. 110 clinical trials using at least 1 PD1/PDL1 inhibitor were found. 11,043 patients were enrolled in interventional arms in these trials. Agents studied were pembrolizumab, atezolizumab, nivolumab, and durvalumab. Only 20 protocols had serious ocular AEs reported to the sponsor. Among those, there were a total of 5,694 serious AEs from the 20 protocols, representing a total of 1,804 patients treated with one of the agents. Toxicity was graded by the investigators and CTEP, as per the Common Terminology Criteria for Adverse Events (CTCAE), published by CTEP and used as a standard in oncology drug development for grading.
Results :
35 ocular adverse events from 27 patients (1.4%) were reported as serious AEs to CTEP. 19/35 ocular AEs had a probable or possible attribution to the PD1 or PDL1 inhibitor. The median CTCAE toxicity grade of these 19 attributed ocular AEs was 2 (moderate). Ocular AEs included: uveitis (3), episcleritis (2), papilledema (2), eye pain (2), blurred vision (2), scleritis, filamentous keratitis, cancer-associated retinopathy, retinal detachment, corneal ulcer, decreased vision, nystagmus, and diplopia.
Conclusions :
Ocular AEs are an uncommon complication of PD1/PDL1 inhibitor therapy. However, when ocular AEs occur, over half (10/19) are potentially vision-threatening. Standardized systems for evaluation and reporting of ocular AEs are needed in future trials to guide physicians.
This is a 2020 ARVO Annual Meeting abstract.