A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin.

INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments. CONCLUSIONS: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs.

Entropion-ectropion: the influence of axial globe length on lower eyelid malposition.

PURPOSE: To evaluate the effect of axial globe length and other biometry parameters on age-related lower eyelid malposition. METHODS: Consecutive patients with involutional lower eyelid malposition underwent preoperative biometry with Zeiss IOL Master and Hertel's exophthalmometer prior to surgery. Patients with other causes of eyelid malposition and thyroid eye disease were excluded. GraphPad InStat was used for t test and chi-square statistical analysis. RESULTS: Data on 57 eyelids of 52 Caucasian patients were collected. There were 28 ectropions and 29 entropions. The mean axial globe length in the ectropion group (23.5 mm, standard deviation ± 0.9) was significantly longer than in the entropion group (22.7 mm, standard deviation ± 1.03) (p = 0.008). There was significant sex predilection, with entropion more common in women and ectropion more common in men (p = 0.03). The mean axial globe projection in the ectropion group was 16.6 mm (standard deviation ± 2.4) and in the entropion group was 14.6 mm (standard deviation ± 2.7) (p = 0.002). There was no statistical difference in age, keratometry, amount of astigmatism, and cylinder axis. CONCLUSION: Involutional eyelid malposition directly correlates with axial globe length with the ectropion group having lengthier eyes compared with the entropion group. Hence, axial globe length could be an influential factor in the onset of involutional eyelid malposition.