Practical clinical management of ocular adverse events related to Antibody-Drug Conjugates in gynaecological malignancies DOI Creative Commons

Bochra Bouguerra Zina,

Frédérique Rousseau,

Stephan Fauquier

и другие.

Cancer Treatment Reviews, Год журнала: 2024, Номер 134, С. 102867 - 102867

Опубликована: Дек. 21, 2024

The advent of Antibody-Drug Conjugates (ADC) represents a significant advancement in targeted therapy for gynaecological malignancies. However, the ocular toxicities associated with ADCs, particularly Tisotumab Vedotin (TV) and Mirvetuximab Soravtansine (MIRV) necessitate effective mitigation order to optimise patient care. This review synthesises findings from clinical trials delineate spectrum adverse events induced by ADCs. analysis focuses on incidence, onset, severity reversibility events. It examines underlying mechanisms toxicity provides management strategies based study protocols. Adverse mainly impact anterior segment, resulting conjunctivitis keratopathy. They affect up 56 % patients treated MIRV 50 60 those receiving TV. Symptoms like blurred vision, dryness pain hinder patient's quality life. Events are CTCAE grade 3 or higher less than 10 cases. median time onset is 1.3 months. may appear months after treatment initiation, indicating need prolonged vigilance. Primary prophylaxis calls local corticotherapy, lubricants some cases, vasoconstrictors. Despite potential severity, most cases reversible transient dose reduction and/or delay. Close monitoring crucial early detection subsequent management. Clinicians ought be cognizant Proactive prophylaxis, education multidisciplinary approach involving ophthalmologists paramount minimising these AEs. Further research essential measure real outcome preventive balance their benefits short long-term risks.

Язык: Английский

Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study DOI
Myung‐Ju Ahn, Kentaro Tanaka, Luis Paz‐Ares

и другие.

Journal of Clinical Oncology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

PURPOSE The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non–small cell lung cancer (NSCLC). METHODS Patients received Dato-DXd 6 mg/kg or 75 mg/m 2 once every 3 weeks. Dual primary end points were progression-free survival (PFS) overall (OS). Objective response rate, duration response, secondary points. RESULTS In total, 299 305 randomly assigned to receive docetaxel, respectively. median PFS was 4.4 months (95% CI, 4.2 5.6) 3.7 2.9 4.2) (hazard ratio [HR], 0.75 [95% 0.62 0.91]; P = .004). OS 12.9 11.0 13.9) 11.8 10.1 12.8), respectively (HR, 0.94 0.78 1.14]; .530). prespecified nonsquamous histology subgroup, 5.5 3.6 0.63 0.51 0.79]) 14.6 12.3 0.84 0.68 1.05]). squamous 2.8 3.9 1.41 0.95 2.08]) 7.6 9.4 1.32 0.91 1.92]). Grade ≥3 treatment-related adverse events occurred 25.6% 42.1% patients, any-grade adjudicated drug-related interstitial disease/pneumonitis 8.8% 4.1% groups, CONCLUSION significantly improved NSCLC, driven by histology. showed a numerical benefit but did not reach statistical significance. No unexpected signals observed.

Язык: Английский

Процитировано

26
Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study DOI Creative Commons
Jacob Sands, Myung‐Ju Ahn, Aaron Lisberg

и другие.

Journal of Clinical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

PURPOSE Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2–directed antibody-drug conjugate with highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142 ) evaluated the safety and clinical activity of Dato-DXd in patients advanced/metastatic non–small cell lung cancer (NSCLC) actionable genomic alterations progressing on or after targeted therapy platinum-based chemotherapy. PATIENTS AND METHODS Patients received 6 mg/kg once every 3 weeks. primary end point was objective response rate (ORR) by blinded independent central review. Secondary points included duration (DOR), safety, tolerability, survival. RESULTS Among 137 who at least 1 dose Dato-DXd, 71.5% three lines prior therapies for disease. Overall, 56.9% had EGFR mutations 24.8% ALK rearrangements. Median treatment 4.4 months (range, 0.7-20.6). confirmed ORR 35.8% (95% CI, 27.8 to 44.4) overall, 43.6% 32.4 55.3) 23.5% 10.7 41.2) those rearrangements, respectively. median DOR 7.0 4.2 9.8), overall disease control 78.8% 71.0 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred 28.5% patients. most common TRAE stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) experienced adjudicated interstitial disease/pneumonitis, (0.7%) 5 event. CONCLUSION Encouraging durable antitumor observed this heavily pretreated NSCLC population alterations. toxicities comparable previous observations, no new signals were observed.

Язык: Английский

Процитировано

9
Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates DOI
Liliana Ascione, Lorenzo Guidi, Ajay Prakash

и другие.

American Society of Clinical Oncology Educational Book, Год журнала: 2024, Номер 44(3)

Опубликована: Июнь 1, 2024

Antibody-drug conjugates (ADCs) have reshaped the cancer treatment landscape across a variety of different tumor types. ADCs' peculiar pharmacologic design combines cytotoxic properties chemotherapeutic agents with selectivity targeted therapies. At present, approval many ADCs used in clinical practice has not always been biomarker-driven. Indeed, predicting activity and toxicity through demonstration specific biomarkers is still great unmet need, identification patients who can derive significant benefit from may often be uncertain. With lack robust predictive to anticipate primary, intrinsic resistance no consolidated aid early (ie, acquired resistance), determination precise biologic mechanisms ADC safety becomes priority quest for better patient-centric outcomes. Of relevance, whether target antigen expression determinant primary clarified, available data remain quite controversial. Antigen assessment typically performed on tissue biopsy, hence only providing information site, therefore unable capture heterogeneous patterns expression. Quantifying all sites would help understand heterogeneity, whereas molecularly characterizing tumor-intrinsic features over time might provide mechanisms. In addition, represent critical concern, since most profile that resembles chemotherapies, unique adverse events requiring special management, possibly because differential pharmacokinetics between small-molecule agent versus payload similar class (eg, deruxtecan conjugate–related interstitial lung disease). As such, potential improve patient selection enrich population likely substantial benefit, especially those disease settings where happen approved competing indications, undefined make decision making unclear how sequence ADCs. this point, clinically actionable space remains top research priority.

Язык: Английский

Процитировано

14
Advances in Trop-2 targeted antibody-drug conjugates for breast cancer: mechanisms, clinical applications, and future directions DOI Creative Commons

Yujun Tong,

Xiaobing Fan, Huan Liu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 1, 2024

Breast cancer remains a leading cause of cancer-related deaths among women worldwide, highlighting the need for novel therapeutic strategies. Trophoblast cell surface antigen 2 (Trop-2), type I transmembrane glycoprotein highly expressed in various solid tumors including all subtypes breast cancer, has emerged as promising target therapy. This review focuses on recent advancements Trop-2-targeted antibody-drug conjugates (ADCs) treatment. We comprehensively analyzed structure and mechanism action ADCs, well role Trop-2 progression prognosis. Several such Sacituzumab Govitecan (SG) Datopotamab Deruxtecan (Dato-DXd), have demonstrated significant antitumor activity clinical trials both triple-negative (TNBC) hormone receptor-positive/HER2-negative (HR+/HER2-) cancer. systematically reviewed ongoing studies these their efficacy safety profiles. Furthermore, we explored potential combining ADCs with other modalities, immunotherapy, targeted therapies, small molecule inhibitors. Notably, shown promise reprogramming tumor microenvironment through multiple signaling pathways, potentially enhancing immunity. aims to provide new insights research directions development innovative offering solutions improve treatment outcomes quality life patients.

Язык: Английский

Процитировано

5
Antibody-drug conjugates in NSCLC with actionable genomic alterations: Optimizing smart delivery of chemotherapy to the target DOI
Giannis Mountzios, Stephanie P.L. Saw, Lizza Hendriks

и другие.

Cancer Treatment Reviews, Год журнала: 2025, Номер 134, С. 102902 - 102902

Опубликована: Фев. 16, 2025

Язык: Английский

Процитировано

0
Toxicities and management strategies of emerging antibody–drug conjugates in breast cancer DOI Creative Commons
Sora Kang, Sung‐Bae Kim

Therapeutic Advances in Medical Oncology, Год журнала: 2025, Номер 17

Опубликована: Янв. 1, 2025

Antibody–drug conjugates (ADCs) offer a promising therapeutic approach for various cancers, enhancing the window while mitigating systemic adverse effects on healthy tissues. ADCs have achieved remarkable clinical success, particularly in treating breast cancer, becoming standard therapy across all subtypes, including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative cancer. Although designed to selectively target antigens via monoclonal antibodies, can exhibit toxicity normal tissues, often due off-target of their cytotoxic payloads. Understanding managing these toxicities according established guidelines are crucial ADC efficacy, minimizing events, ultimately improving patient outcomes. This review comprehensively examines employed cancer treatment explores management strategies. Furthermore, we investigate novel beyond trastuzumab deruxtecan sacituzumab govitecan, evaluating potential efficacy corresponding safety profiles.

Язык: Английский

Процитировано

0
Clinical applications of antibody drug conjugates for gynecologic malignancies: Review of available medicines and emerging therapeutics DOI Creative Commons
Alyssa Bujnak, Samantha Solaru, Krishnansu S. Tewari

и другие.

Gynecologic Oncology, Год журнала: 2025, Номер 195, С. 180 - 191

Опубликована: Март 26, 2025

Язык: Английский

Процитировано

0
Pneumopathies interstitielles diffuses induites par les anticorps conjugués DOI

L Maurier,

Anne‐Laure Chéné,

P. Hulo

и другие.

Revue des Maladies Respiratoires, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Antibody drug conjugates in metastatic brain tumors: current landscape, therapeutic potential and challenges DOI
Stephanie M. Robert,

Allison Toth,

Sapir Lev

и другие.

Journal of Neuro-Oncology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 5, 2025

Язык: Английский

Процитировано

0
Trends in cancer imaging DOI
Xinyuan Zhou,

Binyu Shi,

Gang Huang

и другие.

Trends in cancer, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

2