Personalized medicine: when the common becomes the rare DOI Creative Commons
Daniel O’Connor

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 18, 2024

Historically, much of cancer drug development was predominantly characterized by traditionally described common anatomical tumours with the ability to conduct large well powered randomised clinical trials. The emergence personalised medicine as a discipline and tool, often defined using characterisation individuals' phenotypes genotypes for tailoring right therapeutic strategy person at time, has created new paradigm that offers clear advantages patients in terms their treatment choices but coupled some intrinsic challenges. approach provides opportunities maximise benefits our increasing understanding molecular sciences, diagnostic capabilities, better clinicopathological correlation enhanced abilities pharmacological intervention. However, consequence more targeted approaches trial population programme means it is harder find recruit trials, there are less overall gather data each subset from broader condition, complexity novel products need implement innovative successful evidence generation (Garralda et al., 2019). This Opinion article reflects on impacts this space focus address shifting growing oncology when becomes rare.The impact an increasingly multiple summary include to:• Ensure consistency, efficiency capacity both level health system, additional sponsor have navigate companion or vitro requirements regulations (Lawler 2024) • Demonstrate targetable characteristics defining plausible association tumour, linked way absence these will render medicinal product ineffective population. allows predictive enrichment strategies, where selects subjects who likely respond treatment. helps reduce heterogeneity study power trial. Capture interpret natural history specific pathogenic variants order understand prognostic outcomes determine windows, surrogate endpoints monitor patient Understand regulatory incentive including taking into account varying views global system whether rare histology independent indication considered valid orphan designation, labelling aspects use expedited and/or flexible licensing pathways (Rohr 2023) Determine utilise medicines derived platform technologies (a well-understood reproducible technology which can be adapted than one sharing structural elements standardized manufacturing process) Factor smaller populations making return investment commercial decisions Acknowledge how subsets design, recruitment centre choice, fit expectations decision makers such regulators payersThe subsetting cancers rarer cohorts most impactful nature oncology, particularly choice design feasibility, scientific ethical perspective balance between what might collected pre-market post-market. Such small research requires compromise, programmes involve numbers not possible. Key keep mind objective generating best base through rigorous planning, exploring acceptability methodology (e.g. basket study, adaptive digital twin, synthetic data) difficult strategic uncertainties interpretation single arm utility under-powered approaches). As always, requirement statistical should balanced against drawing clinically relevant scientifically robust conclusions total number eligible may very limited. An acknowledged concern studies susceptible effects variability, missing greater conclusions, policy makers, payers, make data, imply made degree uncertainty. Ultimately exposure equate increased importance emphasis post-market real world collection efficacy safety perspectives. Although great interest potential evidence, application still evolving, meaning essential prospectively discussed payers mechanisms exist (Tafuri 2016).Personalised represents optimised benefit risk patients. These revolutionising (and elsewhere), once conditions subsetted even therapies 'individualised' (O'Connor 2023). rise traditional extrapolation methods, designs solutions, access approval systems. Innovative type help drive efficiencies allow 'scaling up', added inclusion past been neglected (Westphalen 2024).As evolving area, we work together ensure alignment approaches, foster pragmatic acknowledge challenges, helping do miss out 21 st century science advances.

Language: Английский

Comprehensive Genome Profiling for Treatment Decisions in Patients with Metastatic Tumors: Real-World Evidence Meta-Analysis and Registry Data Implementation DOI Creative Commons
Ioannis Zerdes, Panagiotis Filis, Georgios Fountoukidis

et al.

JNCI Journal of the National Cancer Institute, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Background Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges healthcare implementation remain underexplored. Through a meta-analysis of evidence (RWE), we aimed at investigating the applicability clinical comprehensive cancer genome profiling (CGP) patients with metastatic solid tumors. Methods We systematically searched Medline, Embase, Web Science for RWE studies on CGP matched therapies tumors (publication period: 2012—2023). Pooled proportions actionable genomic alterations, treated targeted therapies, treatment, survival outcomes were calculated. Data from Swedish registries used as case-study nationwide implementation. Results Out 7218 identified studies, 144 included our analysis. 59.8% CGP-tested had 15.6% (95% Confidence Interval (CI) 13.4-18.2%) them having received therapy. Objective response was seen 23.9% CI 20.8-27.3%). Overall, CGP-guided treatment correlated prolonged progression-free (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) overall HR 0.60; 0.51-0.70; 21 when compared to conventional treatment. Meta-regression time projections analyses showed that these rates will steadily increase by 2030. Conclusions indicate approximately one-fourth receiving CGP-matched have an objective response. By utilizing meta-regression projections, registry offers insights into potential inform future strategies.

Language: Английский

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The continually evolving landscape of novel therapies in oncogene-driven advanced non-small-cell lung cancer DOI Creative Commons
Barbara Melosky, Rosalyn A. Juergens, Shantanu Banerji

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

Non-small-cell lung cancer (NSCLC) is a highly heterogeneous disease that frequently associated with host of known oncogenic alterations. Advances in molecular diagnostics and drug development have facilitated the targeting novel alterations such majority NSCLC patients driver mutations are now clinically actionable. The goal this review to gain insights into clinical research principles by summary, analysis, discussion data on agents oncogene-driven, advanced beyond those epidermal growth factor receptor (EGFR) anaplastic lymphoma kinase (ALK). A search published presented literature was conducted identify prospective trials integrated analyses reporting outcomes for gene (except EGFR ALK) molecularly selected, NSCLC. Clinical efficacy were extracted from eligible reports summarized text tables. Findings show alteration-directed therapies an extremely active field. Ongoing focuses expansion new both previously identified targets (particularly hepatocyte (MET), human 2 (HER2), Kirsten rat sarcoma viral oncogene homolog (KRAS)) as well novel, potentially actionable (such neuregulin-1 (NRG1) phosphatidylinositol 3-kinase (PI3K)). refinement biomarker selection criteria more selective potent allowing increasingly specific effective advances field resulted large number regulatory approvals over last 3 years. Future developments should focus continued application alteration therapy matching exploration ways target oncogene-driven

Language: Английский

Citations

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Personalisierte Onkologie 2024 – die Sicht der AIO DOI
Annalen Bleckmann, Anke Reinacher‐Schick, C. Benedikt Westphalen

et al.

Forum, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Citations

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Tumor-Agnostic Therapies in Practice: Challenges, Innovations, and Future Perspectives DOI Open Access
Sulin Wu, Rajat Thawani

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 801 - 801

Published: Feb. 26, 2025

This review comprehensively analyzes the current landscape of tumor-agnostic therapies in oncology. Tumor-agnostic are designed to target specific molecular alterations rather than primary site tumor, representing a shift cancer treatment. We discuss recent approvals by regulatory agencies such as FDA and EMA, highlighting that have demonstrated efficacy across multiple types sharing common alterations. delve into trial methodologies underpin these approvals, emphasizing innovative designs basket trials umbrella trials. These present unique advantages, including increased efficiency patient recruitment ability assess drug diverse populations rapidly. However, they also entail certain challenges, need for robust biomarkers complexities requirements. Moreover, we examine promising prospects developing rare cancers exhibit targets typically associated with more prevalent malignancies. By synthesizing insights, this underscores transformative potential It offers pathway personalized treatment transcends conventional histology-based classification.

Language: Английский

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Designing Clinical Trials for Patients With Rare Cancers: Connecting the Zebras DOI
Vivek Subbiah, Megan Othus,

Jim Palma

et al.

American Society of Clinical Oncology Educational Book, Journal Year: 2025, Volume and Issue: 45(3)

Published: April 14, 2025

The field of rare cancer research is rapidly transforming, marked by significant progress in clinical trials and treatment strategies. Rare cancers, as defined the National Cancer Institute, occur fewer than 150 cases per million people each year, yet they collectively represent a portion all diagnoses. Because their infrequency, these cancers pose distinct challenges for trials, including limited patient populations, geographical dispersion, general lack awareness options. Economic limitations further complicate drug development, making initiatives such Orphan Drug Act essential incentivizing research. advent next-generation sequencing (NGS) precision medicine has been instrumental identifying actionable genetic alterations parallel with an explosion development genomically targeted therapies, immunotherapies, antibody conjugates. Advances NGS, medicine, tumor-agnostic therapies have become central to approval drugs, BRAF, NTRK, RET inhibitors, immunotherapy mismatch repair deficient/microsatellite instability–high status highlight potential personalized treatments across diverse types age spectrum. Collaborative from cooperative groups SWOG DART, ASCO TAPUR, NCI-MATCH, pediatric COG-match, DRUP, IMPRESS, innovative registrational basket platform (eg, VE-Basket, ROAR, LIBRETTO-001, ARROW), along advocacy group-run like TRACK, are enhancing access trials. In addition, artificial intelligence improve trial matching process. An integrated approach, combining innovations collaboration multiple stakeholders, crucial advancing research, offering hope better outcomes quality life.

Language: Английский

Citations

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Best of ESMO: pan-tumor highlights DOI Creative Commons
Thorsten Fuereder

memo - Magazine of European Medical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

Citations

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Precision Oncology - Guideline of the Austrian, German and Swiss Societies for Hematology and Medical Oncology DOI Creative Commons
Damian Rieke, Michael Bitzer, Annalen Bleckmann

et al.

European Journal of Cancer, Journal Year: 2025, Volume and Issue: 220, P. 115331 - 115331

Published: Feb. 28, 2025

Language: Английский

Citations

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Efficacy and Safety of Antibody-Drug Conjugates for Lung Cancer Therapy: A Systematic Review of Randomized and Non-Randomized Clinical Trials DOI Creative Commons

Mabel Gallina,

Anna Carollo,

Anna Maria Gallina

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(5), P. 608 - 608

Published: May 3, 2025

Background/Objectives: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-Small-Cell Cancer (NSCLC) accounts for 80–90% all lung cancers. Antibody-Drug Conjugates (ADCs) represent an expanding targeted therapy option treatment NSCLC. The aim to perform a systematic literature review evaluate efficacy and safety profiles ADCs currently undergoing clinical trials Methods: study adhered Preferred Reporting Items Systematic reviews Meta-Analyses (PRISMA) statement. Literature searches were conducted in PubMed, ClinicalTrial.gov Web Science databases, covering period from 2014 2024. Only randomized non-randomized phase II-IV focusing on ADC-based therapies adult patients affected by NSCLC selected. Revised Cochrane Risk-of-Bias Tool Randomized Trials (RoB 2.0) Risk Bias Non-randomized Studies Interventions (ROBINS-I) used overall risk bias included studies, respectively. While GRADE (Grading Recommendations, Assessment, Development Evaluations) methodology was assess certainty evidence. Efficacy endpoints categorized based primary outcomes while assessed through frequency severity Treatment-Emergent Adverse Events (TEAEs), qualitative summary findings conducted. Results: A total seven including three randomized, non-randomized, one without specific allocation, included, comprising 1287 patients, with 693 (54%) men, average age 63 years old. Two studies deemed have low bias, six had moderate or some concerns. Five evaluated: trastuzumab deruxtecan (T-DXd), emtansine (T-DM1), telisotuzumab vedotin, patritumab deruxtecan, datopotamab (Dato-DXd). T-DXd demonstrated superior HER2-overexpressing HER2-mutant NSCLC, ORR 52.9% 49.0%, However, exhibited longer median DOR (16.8 vs. 6.2 months) but higher incidence grade ≥ 3 TEAEs (38.6% 22%). T-DM1 showed modest efficacy, 20% 6.7% patients. Dato-DXd improved (26.4% 12.8%) PFS (4.4 3.7 compared docetaxel. Patritumab achieved 39% EGFR-mutant vedotin limited activity c-MET-positive (ORR 9%, 7.5 months). Frequency varied across ADCs, ILD being major concern, highlighting need strict patient monitoring early intervention mitigate severe adverse events. Conclusions: promising advancement treatment, offering therapeutic options beyond conventional chemotherapy immunotherapy. has emerged as most effective ADC manageable profile, whereas provides viable alternative TROP2-expressing tumors. offer significant benefits, careful selection proactive management events remain crucial. Ongoing future will further refine role personalized potentially their tumor-agnostic use broader populations.

Language: Английский

Citations

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Overcoming barriers to advanced biomolecular technologies that inform treatment of solid tumors: a roadmap to access DOI

Jesús García‐Foncillas,

Arnaud Bayle, Dirk Arnold

et al.

Future Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: May 8, 2025

The advent of advanced biomolecular technologies for detecting molecular and genomic signatures individual tumors has transformed oncology care, introducing proven methodologies that can inform treatment with matched targeted therapies predict response at the patient level. However, access to these been hampered by multiple barriers, most notably price obtainability. Other barriers include lack knowledge available technologies, concerns about value, outdated infrastructures impede critical operations within clinic or laboratory. Accessibility testing are critically important as new technological advances in medicine continue outpace implementation solutions. Given evidence improved outcomes precision medicines, it is imperative understand value afforded technologies. purpose this narrative review describe existing emerging present a "roadmap access" will facilitate urgently needed discussions identify solutions improving access. Implementation raise awareness treatments their prognostic significance, improve collection demonstration fortify clinical laboratory infrastructure operations.

Language: Английский

Citations

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Paving the path towards tissue-agnostic drug approval in oncology DOI
Christophe Le Tourneau, Ivan Bièche, Maud Kamal

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(11), P. 930 - 932

Published: Oct. 24, 2024

Language: Английский

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