Corneal features in trastuzumab emtansine treatment: not a rare occurrence

Deklerck, Els; Denys, Hannelore; Kreps, Elke O.

doi:10.1007/s10549-019-05179-y

Cited by 30 publications

(27 citation statements)

References 15 publications

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“…In a very recent study by Chiang et al [ 5 ], in vivo CLSM revealed a significant reduction in corneal nerve fibers in patients with paclitaxel-induced neuropathy. Moreover, corneal changes detected by in vivo CLSM were also found in breast cancer patients treated with trastuzumab [ 6 , 7 , 8 ].…”

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confidence: 99%

“…In vivo CLSM generates surface-parallel images of the native cornea with cellular resolution, and it can be used to image dendritic cells (DCs) as well as nerves from the subbasal nerve plexus (SNP) with high contrast [ 10 ]. Moreover, several studies have shown that SNP changes are not characteristic of one specific corneal pathology but rather reflect non-specific pathological processes that are present in many corneal, ocular, or systemic diseases [ 11 , 12 , 13 ] or arise as a result of a therapy regime, such as that used to treat multiple myeloma [ 14 ] or breast cancer [ 6 , 7 , 8 ]. Thus, time-lapsed in vivo CLSM-based cell imaging of biomarkers such as corneal sensory nerves or DCs could be a promising tool for the early detection of corneal changes in patients.…”

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confidence: 99%

“…Considering this pivotal role of EGFR and its ligands on the ocular surface, anti-cancer treatments targeting EGFR likely result in corneal complications. The cytotoxicity is probably related to intracellular accumulation of the active metabolite in normal corneal epithelial cells [ 8 , 24 ]. Trastuzumab-mediated ocular adverse effects include a variety of symptoms such as conjunctivitis, dry eye, increased lacrimation, and blurred vision.…”

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confidence: 99%

“…In some recent case reports, progressive corneal ulcerative damage [ 27 ], corneal lesions [ 7 ], and cystoid lesions in deep corneal epithelium [ 6 ] due to treatment with trastuzumab were reported. Most of these adverse effects were described to be stationary and reversible and did not require ocular treatment or cessation of systemic treatment [ 8 ].…”

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confidence: 99%

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Burst of Corneal Dendritic Cells during Trastuzumab and Paclitaxel Treatment

et al. 2021

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During breast cancer therapy, paclitaxel and trastuzumab are both associated with adverse effects such as chemotherapy-induced peripheral neuropathy and other systemic side effects including ocular complications. Corneal nerves are considered part of the peripheral nervous system and can be imaged non-invasively by confocal laser scanning microscopy (CLSM) on the cellular level. Thus, in vivo CLSM imaging of structures of the corneal subbasal nerve plexus (SNP) such as sensory nerves or dendritic cells (DCs) can be a powerful tool for the assessment of corneal complications during cancer treatment. During the present study, the SNP of a breast cancer patient was analyzed over time by using large-scale in vivo CLSM in the course of paclitaxel and trastuzumab therapy. The same corneal regions could be re-identified over time. While the subbasal nerve morphology did not alter significantly, a change in dendritic cell density and an additional local burst within the first 11 weeks of therapy was detected, indicating treatment-mediated corneal inflammatory processes. Ocular structures such as nerves and dendritic cells could represent useful biomarkers for the assessment of ocular adverse effects during cancer therapy and their management, leading to a better visual prognosis.

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confidence: 99%

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confidence: 99%

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Burst of Corneal Dendritic Cells during Trastuzumab and Paclitaxel Treatment

et al. 2021

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“…AGS-16C3F was reported to induce reversible ocular toxicity in patients but not produce a comparable signal in cynomolgus monkeys [ 41 ]. Although most ADCs associated with ocular toxicity contain either MMAF or DM4, ocular toxicities have also been observed for ADCs using MMAE and DM1 [ 42 , 43 ]. For some of these, the ocular effects may involve target expression in the eye; for example, HER2, which is targeted by trastuzumab emtansine, is reportedly expressed in human ocular surface epithelia [ 44 ].…”

Section: Biological Activity Of Drug And/or Antibodymentioning

confidence: 99%

Considerations for the Nonclinical Safety Evaluation of Antibody–Drug Conjugates

Fisher

2021

Antibodies

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The targeted delivery of drugs by means of linking them to antibodies (Abs) to form antibody–drug conjugates (ADCs) has become an important approach in oncology and could potentially be used in other therapeutic areas. Targeted therapy is aimed at improving clinical efficacy while minimizing adverse reactions. The nonclinical safety assessment of ADCs presents several unique challenges involving the need to examine a complex molecule, each component of which can contribute to the effects observed, in appropriate animal models. Some considerations for the nonclinical safety evaluation of ADCs based on a literature review of ADCs in clinical development (currently or previously) are discussed.

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