Real-World Data From a Molecular Tumor Board-Assisted Cancer Care From a Single Center in The Czech Republic: Is Precision Oncology an Accessible Option, or a Privilege for a Minority of Patients?
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články
Grantová podpora
LX22NPO5102
European Union
MUNI/A/1685/2024
Lékařská fakulta, Masarykova univerzita
LM2018132
Ministerstvo Školství, Mládeže a Tělovýchovy
LM2023049
Ministerstvo Školství, Mládeže a Tělovýchovy
FNBr
Ministry of Health
65269705
Ministry of Health
PubMed
40755376
PubMed Central
PMC12319421
DOI
10.1002/cam4.71119
Knihovny.cz E-zdroje
- Klíčová slova
- biomarkers, cancer genetics, next‐generation sequencing, target therapy,
- MeSH
- cílená molekulární terapie MeSH
- dospělí MeSH
- individualizovaná medicína * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory * genetika terapie farmakoterapie mortalita MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Molecular tumor boards (MTBs) support the development of personalized treatment strategies for patients with various cancer types based on comprehensive genomic profiling (CGP) of tumor tissue. Despite the unprecedented results demonstrated in many molecularly driven clinical trials, access to matched therapy remains a significant challenge in routine clinical practice worldwide. METHODS: In this study, we analyzed the MTB cohort from University Hospital Brno in the Czech Republic. Between February 2021 and April 2025, a total of 553 cancer patients with limited therapeutic options underwent CGP of tumor tissue and were subsequently presented at the MTB. RESULTS: The median age of the patients was 61.1 years, and 62.2% were female. The most frequently tested diagnoses were colorectal cancer (n = 88; 15.9%), cholangiocarcinoma (n = 66; 11.9%), and pancreatic cancer (n = 65; 11.8%). The median number of prior lines of standard systemic therapy before CGP testing was two. MTB-recommended matched therapy for 326 (59.0%) out of 553 tested patients, based on 545 unique molecular alterations. The most frequently recommended drugs included immunotherapy (162/545; 29.7%), tyrosine kinase inhibitors (140/545; 25.7%), and poly (ADP-ribose) polymerase inhibitors (63/545; 11.6%). Reimbursement was requested from healthcare insurance providers in 115 cases, with 87 (75.7%) approvals. Together with other reimbursement forms, a total of 96 (17.4%) out of 553 patients initiated matched therapy. A progression-free survival ratio (PFS2/PFS1) of ≥ 1.3 was observed in 29 (41.4%) of the 70 evaluable pretreated patients. CONCLUSION: This is the first study to report on a real-world MTB cohort from the Czech Republic, demonstrating a diagnostic yield comparable to previously published studies, good availability of recommended drugs, and clinical benefit in evaluable patients.
Center for Precision Medicine University Hospital Brno Brno Czech Republic
Center of Excellence CREATIC Faculty of Medicine Masaryk University Brno Czech Republic
Department of Biology Faculty of Medicine CEITEC Masaryk University Brno Czech Republic
Zobrazit více v PubMed
Duan X. P., Qin B. D., Jiao X. D., Liu K., Wang Z., and Zang Y. S., “New Clinical Trial Design in Precision Medicine: Discovery, Development and Direction,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 57, 10.1038/s41392-024-01760-0. PubMed DOI PMC
Drilon A., Laetsch T. W., Kummar S., et al., “Efficacy of Larotrectinib in TRK Fusion‐Positive Cancers in Adults and Children,” New England Journal of Medicine 378, no. 8 (2018): 731–739, 10.1056/NEJMoa1714448. PubMed DOI PMC
Subbiah V., Wolf J., Konda B., et al., “Tumour‐Agnostic Efficacy and Safety of Selpercatinib in Patients With RET Fusion‐Positive Solid Tumours Other Than Lung or Thyroid Tumours (LIBRETTO‐001): A Phase 1/2, Open‐Label, Basket Trial,” Lancet Oncology 23, no. 10 (2022): 1261–1273, 10.1016/S1470-2045(22)00541-1. PubMed DOI PMC
Pant S., Schuler M., Iyer G., et al., “Erdafitinib in Patients With Advanced Solid Tumours With FGFR Alterations (RAGNAR): An International, Single‐Arm, Phase 2 Study,” Lancet Oncology 24, no. 8 (2023): 925–935, 10.1016/S1470-2045(23)00275-9. PubMed DOI PMC
Subbiah V., Sahai V., Maglic D., et al., “RLY‐4008, the First Highly Selective FGFR2 Inhibitor With Activity Across FGFR2 Alterations and Resistance Mutations,” Cancer Discovery 13 (2023): CD‐23‐0475, 10.1158/2159-8290.CD-23-0475. PubMed DOI PMC
Abou‐Alfa G. K., Sahai V., Hollebecque A., et al., “Pemigatinib for Previously Treated, Locally Advanced or Metastatic Cholangiocarcinoma: A Multicentre, Open‐Label, Phase 2 Study,” Lancet Oncology 21, no. 5 (2020): 671–684, 10.1016/S1470-2045(20)30109-1. PubMed DOI PMC
Javle M., Roychowdhury S., Kelley R. K., et al., “Infigratinib (BGJ398) in Previously Treated Patients With Advanced or Metastatic Cholangiocarcinoma With FGFR2 Fusions or Rearrangements: Mature Results From a Multicentre, Open‐Label, Single‐Arm, Phase 2 Study,” Lancet Gastroenterology & Hepatology 6, no. 10 (2021): 803–815, 10.1016/S2468-1253(21)00196-5. PubMed DOI
Subbiah V., Kreitman R. J., Wainberg Z. A., et al., “Dabrafenib Plus Trametinib in BRAFV600E‐Mutated Rare Cancers: The Phase 2 ROAR Trial,” Nature Medicine 29, no. 5 (2023): 1103–1112, 10.1038/s41591-023-02321-8. PubMed DOI PMC
Meric‐Bernstam F., Makker V., Oaknin A., et al., “Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2‐Expressing Solid Tumors: Primary Results From the DESTINY‐PanTumor02 Phase II Trial,” Journal of Clinical Oncology 42, no. 1 (2024): 47–58, 10.1200/JCO.23.02005. PubMed DOI PMC
Marabelle A., Le D. T., Ascierto P. A., et al., “Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair‐Deficient Cancer: Results From the Phase II KEYNOTE‐158 Study,” Journal of Clinical Oncology 38, no. 1 (2020): 1–10, 10.1200/JCO.19.02105. PubMed DOI PMC
Marabelle A., Fakih M., Lopez J., et al., “Association of Tumour Mutational Burden With Outcomes in Patients With Advanced Solid Tumours Treated With Pembrolizumab: Prospective Biomarker Analysis of the Multicohort, Open‐Label, Phase 2 KEYNOTE‐158 Study,” Lancet Oncology 21, no. 10 (2020): 1353–1365, 10.1016/S1470-2045(20)30445-9. PubMed DOI
Suehnholz S. P., Nissan M. H., Zhang H., et al., “Quantifying the Expanding Landscape of Clinical Actionability for Patients With Cancer,” Cancer Discovery 14, no. 1 (2024): 49–65, 10.1158/2159-8290.CD-23-0467. PubMed DOI PMC
Li M. M., Datto M., Duncavage E. J., et al., “Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer,” Journal of Molecular Diagnostics 19, no. 1 (2017): 4–23, 10.1016/j.jmoldx.2016.10.002. PubMed DOI PMC
Massard C., Michiels S., Ferté C., et al., “High‐Throughput Genomics and Clinical Outcome in Hard‐To‐Treat Advanced Cancers: Results of the MOSCATO 01 Trial,” Cancer Discovery 7, no. 6 (2017): 586–595, 10.1158/2159-8290.CD-16-1396. PubMed DOI
Matulonis U. A., Shapira‐Frommer R., Santin A. D., et al., “Antitumor Activity and Safety of Pembrolizumab in Patients With Advanced Recurrent Ovarian Cancer: Results From the Phase II KEYNOTE‐100 Study,” Annals of Oncology 30, no. 7 (2019): 1080–1087, 10.1093/annonc/mdz135. PubMed DOI
Li B. T., Meric‐Bernstam F., Bardia A., et al., “Trastuzumab Deruxtecan in Patients With Solid Tumours Harbouring Specific Activating HER2 Mutations (DESTINY‐PanTumor01): An International, Phase 2 Study,” Lancet Oncology 25, no. 6 (2024): 707–719, 10.1016/S1470-2045(24)00140-2. PubMed DOI
Heinrich K., Miller‐Phillips L., Ziemann F., et al., “Lessons Learned: The First Consecutive 1000 Patients of the CCCMunich PubMed DOI PMC
Kieler M., Unseld M., Bianconi D., et al., “Interim Analysis of a Real‐World Precision Medicine Platform for Molecular Profiling of Metastatic or Advanced Cancers: MONDTI,” ESMO Open 4, no. 4 (2019): e000538, 10.1136/esmoopen-2019-000538. PubMed DOI PMC
Martin‐Romano P., Mezquita L., Hollebecque A., et al., “Implementing the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets in a Comprehensive Profiling Program: Impact on Precision Medicine Oncology,” JCO Precision Oncology 6 (2022): e2100484, 10.1200/PO.21.00484. PubMed DOI
von Hoff D. D., Stephenson J. J., Rosen P., et al., “Pilot Study Using Molecular Profiling of Patients' Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers,” Journal of Clinical Oncology 28, no. 33 (2010): 4877–4883, 10.1200/JCO.2009.26.5983. PubMed DOI
Gladstone B. P., Beha J., Hakariya A., Missios P., Malek N. P., and Bitzer M., “Systematic Review and Meta‐Analysis of Molecular Tumor Board Data on Clinical Effectiveness and Evaluation Gaps,” npj Precision Oncology 9, no. 1 (2025): 96, 10.1038/s41698-025-00865-1. PubMed DOI PMC
Radovich M., Kiel P. J., Nance S. M., et al., “Clinical Benefit of a Precision Medicine Based Approach for Guiding Treatment of Refractory Cancers,” Oncotarget 7, no. 35 (2016): 56491–56500, 10.18632/oncotarget.10606. PubMed DOI PMC
Mock A., Heilig C. E., Kreutzfeldt S., et al., “Community‐Driven Development of a Modified Progression‐Free Survival Ratio for Precision Oncology,” ESMO Open 4, no. 6 (2019): e000583, 10.1136/esmoopen-2019-000583. PubMed DOI PMC
Bertucci F., Gonçalves A., Guille A., et al., “Prospective High‐Throughput Genome Profiling of Advanced Cancers: Results of the PERMED‐01 Clinical Trial,” Genome Medicine 13, no. 1 (2021): 87, 10.1186/s13073-021-00897-9. PubMed DOI PMC
Billon E., Gravis G., Guille A., et al., “Molecular Profiles of Advanced Urological Cancers in the PERMED‐01 Precision Medicine Clinical Trial,” Cancers 14, no. 9 (2022): 2275, 10.3390/cancers14092275. PubMed DOI PMC
Gambardella V., Lombardi P., Carbonell‐Asins J. A., et al., “Molecular Profiling of Advanced Solid Tumours. The Impact of Experimental Molecular‐Matched Therapies on Cancer Patient Outcomes in Early‐Phase Trials: The MAST Study,” British Journal of Cancer 125, no. 9 (2021): 1261–1269, 10.1038/s41416-021-01502-x. PubMed DOI PMC
Kinnersley B., Sud A., Everall A., et al., “Analysis of 10,478 Cancer Genomes Identifies Candidate Driver Genes and Opportunities for Precision Oncology,” Nature Genetics 56, no. 9 (2024): 1868–1877, 10.1038/s41588-024-01785-9. PubMed DOI PMC
Dienstmann R., Garralda E., Aguilar S., et al., “Evolving Landscape of Molecular Prescreening Strategies for Oncology Early Clinical Trials,” JCO Precision Oncology 4 (2020): PO.19.00398, 10.1200/PO.19.00398. PubMed DOI PMC
Normanno N., Apostolidis K., Wolf A., et al., “Access and Quality of Biomarker Testing for Precision Oncology in Europe,” European Journal of Cancer 176 (2022): 70–77, 10.1016/j.ejca.2022.09.005. PubMed DOI
Jain C. K., Srivastava P., Pandey A. K., Singh N., and Kumar R. S., “miRNA Therapeutics in Precision Oncology: A Natural Premium to Nurture,” Exploration of Targeted Anti‐Tumor Therapy 3, no. 4 (2022): 511–532, 10.37349/etat.2022.00098. PubMed DOI PMC