Efficacy and safety of the first-line systemic treatments in patients with advanced-stage urothelial carcinoma: a systematic review and network meta-analysis.

Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC. Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.3.1) was used to perform a network meta-analysis based on the JAGS package and GEMTC package under the Bayesian framework. The main indicators included OS, PFS, ORR and adverse events of grade 3 or higher. This study has been registered in PROSPERO (CRD42024525372). Results: A total of 8 RCTs involving 5539 patients and 12 treatments were included. Pembrolizumab plus Enfortumab Vedotin (PEM+EV) was significantly better than other groups in OS, PFS and ORR. In terms of OS, PEM+EV was significantly better than nivolumab plus platinum-based chemotherapy (NIVO+platinumCT) (HR=0.60; 95% CI: 0.45-0.81), PEM+platinumCT (HR=0.55; 95%CI: 0.42-0.72), atezolizumab (ATE) + platinumCT (HR=0.57; 95%CI: 0.43-0.75) and platinumCT (HR=0.47; 95%CI: 0.38-0.58). In terms of PFS, PEM+EV was also significantly better than NIVO+platinumCT (HR=0.62; 95%CI: 0.48-0.82), PEM+platinumCT (HR=0.58; 95%CI: 0.45-0.74), ATE+platinumCT (HR=0.55; 95%CI: 0.43-0.69) and platinumCT (HR=0.45; 95%CI: 0.38-0.54). In terms of ORR, PEM+EV had a significant be nefit compared with other treatment measures, which was 2.63 times that of platinumCT (OR=2.63; 95%CI: 2.00-3.45). The adverse events of grade 3 or higher in immunotherapy (ATE, PEM, durvalumab) was significantly lower than other treatment measures. Conclusions: PEM+EV can significantly prolong OS and PFS compared with other treatments, and has a higher ORR. The adverse events of grade 3 or higher of ATE was the lowest. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024525372, identifier CRD42024525372.

The role of antibody therapies in treating relapsed chronic lymphocytic leukemia: a review.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adult patients. The landscape of CLL therapy has changed in the last decades with the introduction of antibody-based therapies and novel targeted agents resulting in improved outcomes. AREAS COVERED: This article describes the use of monoclonal antibodies, bispecific antibodies and antibody-drug conjugates in the treatment of relapsed and refractory CLL. The mechanism of action and clinical applications and safety of antibody-based therapies, both as monotherapy and in combination with other drugs, are discussed. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles. EXPERT OPINION: Antibody-based therapeutic strategies have drastically changed the treatment of CLL, as they have introduced the concept of boosting immune responses against tumor cells. While immunotherapy is generally effective, some treatment failure can occur due to antigen loss, mutation, or down-regulation, and this remains the main obstacle to cure. The development of novel antibody therapies, including their combinations with targeted drugs and bispecific antibodies, might help to reduce toxicity and improve efficacy.

Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

BACKGROUND: Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). METHODS: PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. RESULTS: From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 - 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS. CONCLUSIONS: In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.

Pre-treatment [18F]FDG PET/CT biomarkers for the prediction of antibody-drug conjugates efficacy in metastatic breast cancer.

PURPOSE: This study aimed to evaluate the association between pretreatment [18F]FDG PET/CT-derived biomarkers and outcomes in metastatic breast cancer (mBC) patients treated with antibody-drug conjugates (ADCs) Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd). METHODS: A retrospective bicentric analysis was conducted on triple-negative mBC (mTNBC) patients treated with SG and HER2-low mBC patients treated with T-DXd, who underwent [18F]FDG PET/CT scans before therapy. Key biomarkers, including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV) and maximum tumor dissemination (Dmax), were measured. Their prognostic value for progression-free survival (PFS) and overall survival (OS) was assessed using Cox models and Kaplan-Meier curves. RESULTS: 128 patients were included: 71 mTNBC treated with SG and 57 HR-positive and -negative HER2-low mBC treated with T-DXd. Median follow-up was 12.9 months. In the SG cohort, median PFS and OS were 4.8 and 8.9 months, respectively. High Dmax (HR 2.1, 95% CI 1.1-4.3) and high TMTV (HR 2.9, 95% CI 1.2-6.6) were independently associated with shorter OS. In the T-DXd cohort, median PFS and OS were 5.8 and 9.0 months, respectively. High Dmax (HR 2.1, 95% CI 1.2-3.9) and high TMTV (HR 2.4, 95% CI 1.0-6.5) independently correlated with shorter PFS and shorter OS, respectively. CONCLUSION: Pretreatment [18F]FDG PET/CT-derived biomarkers, namely TMTV and Dmax, have significant prognostic value in patients with mTNBC and HER2-low mBC treated with SG and T-DXd. These biomarkers improve prognostic prediction and may optimize treatment strategies, warranting their clinical use, but larger studies are needed to validate these findings.

Therapeutic antibodies in oncology: an immunopharmacological overview.

The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer.

Understanding the chemistry & pharmacology of antibody-drug conjugates in triple-negative breast cancer with special reference to exatecan derivatives.

In the spectrum of breast malignancies, triple-negative breast cancer is the most widely spreading subtype of breast cancer due to a low availability of therapeutic remedies. Recently, antibody-drug conjugates dramatically resolved the landscape for the treatment of triple-negative breast cancer. This review mainly focuses on the chemistry, structure, mechanism of action, and role of antibody-drug conjugates in triple-negative breast cancer. Datopotecan Deruxtecan (Dato-DXd) is a new-generation ADC showing encouraging results for TNBC. In this review, we have also emphasized TROP-2-directed Datopotamab deruxtecan ADCs to treat triple-negative breast cancer, its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, adverse events, and their ongoing clinical trials.

Overcoming limitations and advancing the therapeutic potential of antibody-oligonucleotide conjugates (AOCs): Current status and future perspectives.

As cancer incidence rises due to an aging population, the importance of precision medicine continues to grow. Antibody-drug conjugates (ADCs) exemplify targeted therapies by delivering cytotoxic agents to specific antigens. Building on this concept, researchers have developed antibody-oligonucleotide conjugates (AOCs), which combine antibodies with oligonucleotides to regulate gene expression. This review highlights the mechanism of AOCs, emphasizing their unique ability to selectively target and modulate disease-causing proteins. It also explores the components of AOCs and their application in tumor therapy while addressing key challenges such as manufacturing complexities, endosomal escape, and immune response. The article underscores the significance of AOCs in precision oncology and discusses future directions, highlighting their potential in treating cancers driven by genetic mutations and abnormal protein expression.

Developing combination therapies with biologics in triple-negative breast cancer.

INTRODUCTION: Novel compounds have entered the triple-negative breast cancer (TNBC) treatment algorithm, namely immune checkpoints inhibitors (ICIs), PARP inhibitors and antibody-drug conjugates (ADCs). The optimization of treatment efficacy can be enhanced with the use of combination treatments, and the incorporation of novel compounds. In this review, we discuss the combination treatments under development for the treatment of TNBC. AREAS COVERED: The development of new drugs occurring in recent years has boosted the research for novel combinations to target TNBC heterogeneity and improve outcomes. ICIs, ADCs, tyrosine kinase inhibitors (TKIs), and PARP inhibitors have emerged as leading players in this new landscape, while other compounds like novel intracellular pathways inhibitors or cancer vaccines are drawing more and more interest. The future of TNBC is outlined in combination approaches, and based on new cancer targets, including many chemotherapy-free treatments. EXPERT OPINION: A large number of TNBC therapies have either proved clinically ineffective or weighted by unacceptable safety profiles. Others, however, have provided promising results and are currently in late-stage clinical trials, while a few have actually changed clinical practice in recent years. As novel, more and more selective drugs come up, combination strategies focusing the concept of synergy are fully warranted for the future.

Recent advances in targeted drug delivery systems for multiple myeloma.

Despite significant therapeutic advances, multiple myeloma (MM) remains a challenging, incurable, hematological malignancy. The efficacy of traditional chemotherapy and currently available anti-MM agents is in part limited by their adverse effects, which restrict their therapeutic potential. Nanotherapeutics is an emerging field of cancer therapy that can overcome the biological and chemical barriers of existing anticancer drugs. This review presents an overview of recent advancements in nanoparticle- and immunotherapy-based drug delivery systems for MM treatment. It further delves into the targeting strategies, mechanism of controlled drug release, and challenges associated with the development of drug delivery systems for the treatment of MM.

Safety and efficacy of antibody-drug conjugates plus immunotherapy in solid tumours: A systematic review and meta-analysis.

BACKGROUND: Combining antibody-drug conjugate (ADCs) with immune checkpoint inhibitors (ICIs) is emerging as a promising treatment option to increase efficacy outcomes. However, concerns arise regarding the safety of these combinations, as some toxicities may overlap. Currently, there is still limited information about the safety profiles of this strategy. METHODS: A systematic review and meta-analysis was conducted to identify clinical trials investigating FDA-approved ADCs in combination with ICI drugs in the metastatic setting across all solid tumors. The primary endpoint of this study was the percentage of adverse events (AEs) of any grade and grade ≥ 3. Secondary endpoints include the percentage of patients with AEs leading to death, treatment discontinuation, proportion of complete responses (CR) and overall response rate (ORR). A parallel search was conducted to quantify the safety profile of ADCs and ICIs in monotherapy. Random effects models were used to estimate pooled outcomes. RESULTS: Sixteen trials involving 1,133 patients treated with ADC plus ICI met the inclusion criteria with six different ADCs evaluated. Overall, 55.3 % of patients developed grade ≥ 3 AEs, 30.0 % of patients had treatment discontinuation, and 3.0 % experienced AEs leading to death. When compared to trials evaluating ADC or ICI as monotherapy, the combination results in similar rates of the most common AEs. However, it increases the risk of specific toxicities, such as ILD/pneumonitis (15.0 % with T-DXd plus ICI vs. 11.5 % with T-DXd alone). The pooled ORR was 48.8 % (95 %CI 39.4 % - 58.4 %) and the CR rate was 9.0 % (95 %CI 5.5 - 14.5). PD-L1-positive tumors showed numerically better efficacy outcomes. CONCLUSIONS: This meta-analysis shows that the safety profile of the ADC plus ICI is comparable to that of ADC monotherapy. However, it increases the risk of certain toxicities of special interest, such as ILD/pneumonitis, highlighting the need for careful monitoring.

Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses.

BACKGROUND: Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity. METHODS: This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E. RESULTS: Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress. CONCLUSION: In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.

ADC: a deadly killer of platinum resistant ovarian cancer.

Platinum is a key component of ovarian cancer systemic therapy. However, most patients will eventually face a recurrence, leading to chemotherapy resistance, especially against platinum. For individuals with platinum-resistant ovarian cancer (PROC), treatment options are limited, and their survival prospects are grim. The emergence of antibody-drug conjugates (ADCs) shows promises as a future treatment for PROC. This review synthesizes current research on the effectiveness of ADCs in treating PROC. It encapsulates the advancements and clinical trials of novel ADCs that target specific antigens such as Folate Receptor alpha (FRα), MUC16, NaPi2b, Mesothelin, Dipeptidase 3(DPEP3), and human epidermal growth factor receptor 2 (HER2), as well as tissue factor, highlighting their potential anti-tumor efficacy and used in combination with other therapies. The ADCs landscape in ovarian cancer therapeutics is swiftly evolving, promising more potent and efficacious treatment avenues.

Ocular toxicities of FDA-approved antibody drug conjugates.

Antibody-drug conjugates (ADCs) are an emerging field of cancer treatments that are becoming more widespread in their use. However, there are potential ocular toxicities associated with these drugs that ophthalmologists need to be aware of to better maintain ocular health as patients undergo rigorous medical treatment for their conditions. While many ADCs have been approved by the Food and Drug Administration (FDA), many subsequent reports have been published regarding additional ocular side effects these drugs may cause. This review provides ophthalmologists with a practical guide on how to treat ocular toxicities associated with all FDA-approved ADCs to date. The potential pathophysiology of side effects is also discussed.

Cardiac toxicity of HER-2 targeting antibody-drug conjugates: overview and clinical implications.

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

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Review of Dose Justifications for Antibody-Drug Conjugate Approvals from Clinical Pharmacology Perspective: a Focus on Exposure-Response Analyses.

Antibody-drug conjugates (ADCs) are revolutionizing cancer treatment by specific targeting of the cancer cells thereby improving the therapeutic window of the drugs. Nevertheless, they are not free from unwanted toxicities mainly resulting from non-specific targeting and release of the payload. Therefore, the dosing regimen must be optimized through integrated analysis of the risk-benefit profile, to maximize the therapeutic potential. Exposure-response (E-R) analysis is one of the most widely used tools for risk-benefit assessment and it plays a pivotal role in dose optimization of ADCs. However, compared to conventional E-R analysis, ADCs pose unique challenges since they feature properties of both small molecules and antibodies. In this article, we review the E-R analyses that have formed the key basis of dose justification for each of the 12 ADCs approved in the USA. We discuss the multiple analytes and exposure metrics that can be utilized for such analysis and their relevance for safety and efficacy of the treatment. For the endpoints used for the E-R analysis, we were able to uncover commonalities across different ADCs for both safety and efficacy. Additionally, we discuss dose optimization strategies for ADCs which are now a critical component in clinical development of oncology drugs.

Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action.

BACKGROUND: Lung cancer remains a critical public health issue, presenting multifaceted challenges in prevention, diagnosis, and treatment. This article aims to review the current landscape of lung cancer research and management, delineate the persistent challenges, and outline pragmatic solutions. MATERIALS AND METHODS: Global experts from academia, regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the National Cancer Institute (NCI), professional societies, the pharmaceutical and biotech industries, and patient advocacy groups were gathered by the New York Lung Cancer Foundation to review the state of the art in lung cancer and to formulate calls to action. RESULTS: Improving lung cancer management and research involves promoting tobacco cessation, identifying individuals at risk who could benefit from early detection programs, and addressing treatment-related toxicities. Efforts should focus on conducting well-designed trials to determine the optimal treatment sequence. Research into innovative biomarkers and therapies is crucial for more personalized treatment. Ensuring access to appropriate care for all patients, whether enrolled in clinical trials or not, must remain a priority. CONCLUSIONS: Lung cancer is a major health burden worldwide, and its treatment has become increasingly complex over the past two decades. Improvement in lung cancer management and research requires unified messaging and global collaboration, expanded education, and greater access to screening, biomarker testing, treatment, as well as increased representativeness, participation, and diversity in clinical trials.

Site-specific Quadruple-Functionalised Antibodies.

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents that have yielded striking clinical successes. However, the efficacy of ADCs often suffers from issues associated with tumor heterogeneity and resistance. To overcome these problems, a new generation of ADCs comprising a single monoclonal antibody with multiple different payloads attached, termed multi-payload ADCs, have been developed. Here we deploy multiple orthogonal site-specific protein modification strategies to generate highly homogeneous multi-functionalised antibody conjugates comprising up to four different functionalities installed at four unique sites on the antibody. This work, which includes the use of a site-specific cyclopropenone (CPO)-based reagent, represents the first example of a homogeneous multi-payload ADC with a payload count greater than two, and thereby facilitates the development of the next generation of ADCs.

Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma.

Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody-drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.

Antibody drug conjugates in recurrent or metastatic cervical cancer: a focus on tisotumab vedotin state of art.

Cervical cancer (CC) is still characterized by a poor prognosis despite the progress made in its treatment in recent years. Although immunotherapy has improved outcomes for advanced/recurrent disease, there is a significant gap in addressing patients' needs when they progress after platinum and immunotherapy treatments. In this setting, traditional chemotherapy showed limited effectiveness. In this context, antibody-drug conjugates (ADCs) emerged as a promising tool within targeted cancer therapies. Tisotumab vedotin (TV), an ADC targeting tissue factor, represents the first ADC approved by the US Food and Drug Administration for the treatment of recurrent or metastatic CC with disease progression on or after chemotherapy. In phase I-III published trials, TV has already demonstrated an advantage in terms of objective response rate (17.8%-54.4%) and progression-free survival (3.1-6.9 months) in patients who progressed to the first-line standard therapy. Data concerning the addition of TV to platinum/pembrolizumab first-line chemotherapy are still under analysis and strongly expected. However, several questions are still unresolved: (1) the identification of the most suitable timing for ADCs administration in the treatment sequence of advanced/recurrent CC; (2) the evaluation of combination therapies as a tool to minimize the emergence of resistant clones and to enhance overall effectiveness; and (3) the assessment of tolerability and correct management of special toxicities (e.g. ocular and neurological adverse events). In the near future, an improvement in patient selection via biomarker-driven strategies should be crucial for optimizing both treatment benefits and maintaining an acceptable toxicity profile.

Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA adverse event reporting system (FAERS).

Background: Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database. Methods: Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated. Results: A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26-1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2-24.58)], dry eye [ROR = 9.69, 95% CI (8.81-10.66)], night blindness [ROR = 259.87, 95% CI (228.23-295.89)], vision blurred [ROR = 1.78, 95% CI (1.57-2.02)], photophobia [ROR = 10.45, 95% CI (9.07-12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88-27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3-178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66-156.69)], eye disorder [ROR = 2.71, 95% CI (2.21-3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days. Conclusion: ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.