e15001 Background: Ocular toxicities are common challenges associated with anticancer agents, including small molecules, antibody-drug conjugates (ADC), targeted antibodies, particularly those targeting Epidermal Growth Factor Receptor (EGFR), Mitogen-activated protein kinase (MEK) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). This subject suffers from a paucity of consensus guidelines, especially drug class versus severity of toxicity versus ocular anatomy. The aim of this paper is to examine the ocular side effects of various classes of anticancer therapies. Methods: Approved anticancer drugs known to be associated with ocular toxicity were reviewed as of Dec-2021. US FDA Labels were reviewed, as were further publications on said drugs. Ocular toxicities were then classified based on the anatomy of the eye, class of drug and drug target, severity and the recommended surveillance and management. Results: The most common ocular toxicities were mild including “visual disturbances” and conjunctivitis. Severe toxicities were reported as well, including corneal ulceration, retinal vascular occlusion, optic neuritis, and even cortical blindness. Our review clearly indicates that each class of drugs has a distinct ocular toxicity pattern, including the precise segment of the eye involved, severity and pattern of manifestation. Drug related toxicity involving the anterior segment tends to be of lesser severity, whereas posterior segment toxicity is more severe, and, as such, may result in treatment interruptions. Molecular-pathway-specific toxicity patterns were noted. EGFR inhibitors were associated with corneal-ulceration and microcysts. MEK inhibitor-associated retinopathy (MEKAR) is documented, and drugs (e.g. Trametinib) increase the risk of retinal detachment and retinal vascular occlusion. We noted a pattern of Monoclonal Antibodies (e.g. Cetuximab) having lower adverse events than the small molecule (e.g. Gefitinib) having the similar pathway of action. ADCs (12 US FDA approved) are known to affect various ocular tissues, commonly involving the ocular surface, with intra-class differences. Conclusions: Our review highlights the need for an ophthalmic referral at baseline, prior to initiating anticancer drugs known to cause ocular toxicities. Cancer patients need consensus-based multidisciplinary global standardized algorithms for surveillance, early diagnosis and management of ocular toxicities associated with anticancer therapies.
e18699 Background: DIILD accounts for 3-5% of all ILD cases, with Anticancer agents accounting for 23-51% of all cases, and Case-Fatality Rates of 51.3%. Guidelines for anticancer therapy-related DIILD are lacking. DIILD was not often identified as an adverse event until late in drug development or after launch. Methods: Publications till Feb 2023 were reviewed for incidence, time to onset, prevention and early identification of anticancer DIILD. Results: Highest reportedincidence of DIILD was associated with targeted therapies [mTOR Inhibitors (9.5- 58%), Anti-EGFR (0.9 - 5.9%), MEK inhibitors (2.4%), CDK 4/6 inhibitors (1.6%), PARP inhibitors (0.79%)]; Chemotherapy [Bleomycin (6.8-21%), Gemcitabine(1.1-3.9%), Irinotecan (0.74%)]; ADCs (11.4%); CTLA4 inhibitors (5.44%); and Check-point inhibitors [(CPIs: 1.1-3.6%), PD-1 inhibitors (3.6%), PD-L1 inhibitors (1.3%)]. The rates of DIILD were higher in combinations compared to single-agents. Higher Mortality rates were associated with Anti-EGFR (18-51.3%), Irinotecan (24%), Bleomycin (8.1-23%), Gemcitabine (0-22%), mTOR Inhibitors (0-20%), Check-point inhibitors (all CPIs: 8-9.4%). The time of onset was as early as a week for CPIs (42% occurred within first two months), 28 days for EGFR:TKIs, 60-172 days for MEK Inhibitors, and 14-638 days for ADCs. Risk-mitigation strategies for DIILD: Identification of high-risk patients – (multiple prior lines of therapy, combination therapy, lung comorbidities, poor respiratory reserve, smokers). Early radiological diagnosis accompanied by Monitoringfor early signs of ILD with wearable technology. Conclusions: Research in Genomics and biomarkers to identify patients at risk, development of Artificial Intelligence (AI) algorithms for PFT interpretation, early radiological detection and audiometry analysis are ongoing and urgently needed.
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