Ocular Side Effects of EGFR-Inhibitor ABT-414 in Recurrent Glioblastoma: A Long-Term Safety Study

Abstract

This study aimed to prospectively evaluate, on a long-term basis, corneal side effects secondary to compassionate administration of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in patients affected by EGFR-amplified recurrent glioblastoma. Fifteen patients with a median follow-up of 4.3 months after treatment discontinuation were enrolled. Each patient underwent full ophthalmologic examination including in vivo corneal confocal microscopy (CCM). No CTCAE grade 4 toxicity and four (27%) grade 3 toxicities were documented during treatment. Ocular symptoms (blurred vision, eye pain, photophobia) were experienced by all patients, reaching maximal severity after the second ABT-414 infusion, with persistence until treatment discontinuation. During treatment, CCM documented specific changes in the corneal epithelium and in the sub-basal nerve plexus layer fibers of all eyes. The median time of symptoms resolution after treatment discontinuation ranged from 38 days (eye pain) to 53 days (photophobia). The median time of signs resolution ranges from 14 days (corneal ulcer) to 38 days (superficial punctate epitheliopathy, corneal stroma edema and intraepithelial cysts). ABT-414 corneal side effects are detectable in all treated patients. Related symptoms are gradually experienced by all patients during treatment and although reversible, they are characterized by a relative prolonged persistence after treatment discontinuation.

Corneal Findings Associated to Belantamab-Mafodotin (Belamaf) Use in a Series of Patients Examined Longitudinally by Means of Advanced Corneal Imaging

“…Remarkably, other off-label drugs previously adopted for the treatment of MM were shown to induce corneal epithelial alterations, probably resulting from drug accumulation in the epithelium and subsequent cellular apoptosis. Among these, depatuximab mafoditin, which acts as an epidermal growth factor receptor inhibitor, caused a reversible corneal epitheliopathy in treated patients, characterized by multiple and diffuse hyper-reflective spots, progressive sub-basal nerve plexus fragmentation and by the appearance of cystic structures at the level of corneal epithelium [ 8 , 9 , 10 ].…”

Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)

“…An increased expertise regarding the management of Depatux-M has been gained by neuro-oncologists which have previously participated in the INTELLANCE 1 and 2 trials; another key factor contributing the management of ocular toxicity is that all patients enrolled in our study were followed by a dedicated ophthalmologist. Indeed, it was already demonstrated that the ocular side effects caused by Depatux-M can be reversible and moderate if carefully managed [ 19 , 20 ]. In our study, Depatux-M dose reduction occurred in 17% of patients versus 12% reported in the previous phase 1 study, while dose delays occurred in only 28% versus the 58% seen in the prior study [ 15 ].…”

Glioblastoma pharmacotherapy: A multifaceted perspective of conventional and emerging treatments (Review)

“…Among these, the following are of interest: i) Molecularly targeted therapy; ii) anti-angiogenic drugs; iii) GSC targeting; iv) microRNAs; v) immunotherapy; vi) nanotherapy; vii) gene therapy; and viii) oncolytic viruses (59). As of 2021, a number of compounds have successfully gone through all phases of drug development and have been approved for clinical testing on human subjects (21,37,38,42,44,54,60,61,(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82). They are summarized in Table II.…”

“…In the era of precision medicine, a combination of molecular techniques can also be applied to target the unique tumour characteristics of individual patients (18)(19)(20). To improve the outcome, a comprehensive list of parameters must be understood, including the GBM microenvironment, the pharmacokinetic and pharmacodynamic profiles of the drug of interest, in addition to the delivery and safety profiles (21). Although some drugs (TMZ, lomustine, carmustine and bevacizumab) have obtained Food and Drug Administration (FDA) approval for GBM treatment, others are currently at different stages of clinical trial testing (22).…”