Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study

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

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Injecting hope: the potential of intratumoral immunotherapy for locally advanced and metastatic cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity known used, they often fail to achieve satisfactory long-term patient outcomes survival. Recently, immunotherapy has shown success patients by harnessing important interactions between immune system cancer. However, many these therapies lead frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, severe cases, fatalities. New approaches like intratumoral immunotherapy, characterized reduced effects, cost, systemic toxicity, offer promising prospects for future applications clinical oncology. In context locally metastatic cancer, combining diverse immunotherapeutic other targeting multiple cancer hallmarks appears crucial. Such combination hold promise improving survival promoting a sustained response. This review aims provide overview approaches, specifically focusing on administration drugs cancers. It also explores integration modalities maximize Additionally, summarizes recent advances discusses novel outlining directions field.

Language: Английский

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Artificial intelligence-based biomarkers for treatment decisions in oncology

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The development of new therapeutic strategies such as immune checkpoint inhibitors (ICIs) and targeted therapies has increased the complexity treatment landscape for solid tumors. At current rate annual FDA approvals, potential options could increase by tenfold over next 5 years. cost personalized medicine technologies limits its accessibility, thus increasing socioeconomic disparities in treated population. In this review we describe artificial intelligence (AI)-based solutions - including deep learning (DL) methods routine medical imaging large language models (LLMs) electronic health records (EHRs) to support cancer decisions with cost-effective biomarkers. We address limitations these propose steps towards their adoption clinical practice.

Language: Английский

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Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non–Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA

Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 29(17), P. 3340 - 3351

Published: June 28, 2023

Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be to predict outcomes.This was a retrospective, exploratory of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm; ex19del or L858R) NSCLC; AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), comparator EGFR-tyrosine kinase inhibitor (EGFR-TKI; gefitinib/erlotinib; FLAURA), platinum-based doublet chemotherapy (AURA3) given. EGFRm analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed detectable/non-detectable plasma clearance (non-detection) 3/6.In (n = 291), non-detectable versus detectable longer median progression-free survival [mPFS; HR, 0.48; 95% confidence interval (CI), 0.33-0.68; P < 0.0001]. In with Week 3 non-clearance 184), respectively, mPFS (months; CI) 10.9 (8.3-12.6) 5.7 (4.1-9.7) osimertinib 6.2 (4.0-9.7) 4.2 (4.0-5.1) platinum-pemetrexed. 499), (HR, 0.54; CI, 0.41-0.70; 0.0001). For 334), 19.8 (15.1 not calculable) 11.3 (9.5-16.5) 10.8 (9.7-11.1) 7.0 (5.6-8.3) EGFR-TKI. Similar outcomes observed 6 clearance/non-clearance.Plasma as early weeks on-treatment has the potential in

Language: Английский

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