Implementing digital pathology: qualitative and financial insights from eight leading European laboratories DOI Creative Commons
Xavier Matías‐Guiu, Jordi Temprana‐Salvador, Pedro Carríón López

et al.

Virchows Archiv, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Abstract Digital Pathology (DP) revolutionizes the diagnostic workflow. Digitized scanned slides enhance operational efficiency by facilitating remote access, slide storage, reporting and automated AI image analysis, enabling collaboration research. However, substantial upfront maintenance costs remain significant barriers to adoption. This study evaluates DP’s financial qualitative value, exploring whether long-term benefits justify investments addressing implementation challenges in large public private European laboratory settings. A targeted literature review, semi-structured interviews, surveys, a net present value (NPV) model were employed assess impact on clinical practice financials. Qualitative findings validate key of DP, including optimized workflow, enhanced logistics, improved organization. Pathologists reported smooth integration, training, teaching, research capabilities, increased flexibility through work. Collaboration within multidisciplinary teams was strengthened, while case examination access archival notably improved. Quantitative results indicate that DP demonstrates strong potential, achieving cost recovery 6 years. investment 7-year NPV + €0.21 million (m) driven productivity diagnosis volumes. Although high for scanners, system integration pose barrier adoption larger institutions are better positioned leverage economies scale. underscores importance sustained support cope with initial regional driving widespread DP. Expanding reimbursement policies pathology procedures could significantly reduce barriers.

Language: Английский

Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study DOI Creative Commons
Aditya Bardia, Ian E. Krop, Takahiro Kogawa

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(19), P. 2281 - 2294

Published: April 23, 2024

Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to potent, exatecan-derived topoisomerase I inhibitor payload via plasma-stable, selectively cleavable linker.

Language: Английский

Citations

61
Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein–Overexpressing Advanced Nonsquamous EGFR-Wildtype Non–Small Cell Lung Cancer in the Phase II LUMINOSITY Trial DOI
D. Ross Camidge, Jair Bar, Hidehito Horinouchi

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(25), P. 3000 - 3011

Published: June 6, 2024

Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment Teliso-V (stage I) and expand selected group efficacy evaluation II). Stage enrolled patients nonsquamous epidermal growth factor receptor (

Language: Английский

Citations

34
BL-B01D1, a first-in-class EGFR–HER3 bispecific antibody–drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study DOI
Yuxiang Ma, Yan Huang, Yuanyuan Zhao

et al.

The Lancet Oncology, Journal Year: 2024, Volume and Issue: 25(7), P. 901 - 911

Published: May 29, 2024

Language: Английский

Citations

30
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

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 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.

Language: Английский

Citations

25
Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor–Positive Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: Primary Results From TROPION-Breast01 DOI
Aditya Bardia, Komal Jhaveri, Seock‐Ah Im

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ cancer, who had disease progression on endocrine therapy, for whom therapy was unsuitable, and received one to two previous lines setting, were randomly assigned 1:1 Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points progression-free survival (PFS) by blinded independent central review (BICR) overall (OS). RESULTS Patients (n = 365) 367). significantly reduced risk death (PFS BICR hazard ratio [HR], 0.63 [95% CI, 0.52 0.76]; P < .0001). Consistent PFS benefit observed across subgroups. Although OS data not mature, a trend favoring (HR, 0.84 0.62 1.14]). rate grade ≥3 treatment-related adverse events (TRAEs) lower than (20.8% v 44.7%). most common TRAEs (any grade; ≥3) nausea (51.1%; 1.4%) stomatitis (50%; 6.4%) neutropenia (grouped term, 42.5%; 30.8%) ICC. CONCLUSION receiving statistically significant clinically meaningful improvement favorable manageable safety profile, compared Results support as novel treatment option cancer have this setting.

Language: Английский

Citations

22
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

et al.

Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

8
Emerging Targeted Therapies in Non-Small-Cell Lung Cancer (NSCLC) DOI Open Access

Syeda A. Mina,

Mohamed Shanshal, Konstantinos Leventakos

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 353 - 353

Published: Jan. 22, 2025

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages cancer. Newer advances in common novel oncogenic drivers continue occur at vigorous speed, making it challenging stay up date with rapidly evolving field. In this article, we review emerging perspectives actionable targets We focus on development newer KRAS-directed therapies, particularly non-G12C mutations, pan-RAS inhibitors, RAS-GTP inhibitors. also describe current standard care for EGFR- ALK-altered NSCLC dive into treatments expected be clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, FGFR alterations as Finally, conclude body evidence targeting TROP-2 a target, potentially importance post-targeted therapy scenarios.

Language: Английский

Citations

2
Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan DOI Creative Commons
Rebecca S. Heist, Jacob Sands, Aditya Bardia

et al.

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 125, P. 102720 - 102720

Published: March 11, 2024

Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery cytotoxic agents tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising topoisomerase I inhibitor payload monoclonal antibody directed trophoblast cell-surface antigen 2 (TROP2), protein that broadly expressed in several types solid tumors. Dato-DXd being investigated across multiple indications. In ongoing, first-in-human TROPION-PanTumor01 phase study (ClinicalTrials.gov: NCT03401385), encouraging durable antitumor activity manageable safety profile was demonstrated patients advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2– BC), triple-negative (TNBC), non-small cell lung (NSCLC). Improved understanding adverse events (AEs) associated their optimal management essential ensure safe successful administration. Interstitial disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, ocular surface have been identified as AEs special interest (AESIs) for which appropriate prevention, monitoring, essential. This article summarizes incidence AESIs among HR+/HER2 − BC, TNBC, NSCLC reported TROPION-PanTumor01. We report our recommendations AESI prophylaxis, early detection, management, using experience gained from treating occur clinical trials.

Language: Английский

Citations

16
Trop2-targeted therapies in solid tumors: advances and future directions DOI Creative Commons
Xinlin Liu,

Leina Ma,

Jiyixuan Li

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(9), P. 3674 - 3692

Published: Jan. 1, 2024

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, rapid development various Trop2-targeted therapies, notably marked by advent antibody-drug conjugate (ADC), revolutionized outcome for patients facing Trop2-positive with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides comprehensive summary advances including ADCs, antibodies, multispecific agents, immunotherapy, vaccines, small molecular inhibitors, along in-depth discussions on their designs, mechanisms action (MOAs), limitations. Additionally, we emphasize clinical research progress these emerging focusing application efficacy against tumors. Furthermore, propose directions future research, enhancing our understanding Trop2's structure biology, exploring best combination strategies, tailoring precision based Trop2 testing methodologies.

Language: Английский

Citations

13
Antibody–drug conjugates in lung and breast cancer: current evidence and future directions—a position statement from the ETOP IBCSG Partners Foundation DOI
Solange Peters, Sherene Loi, Fabrice André

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(7), P. 607 - 629

Published: April 21, 2024

Language: Английский

Citations

9