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?

. 2025 Aug ; 14 (15) : e71119.

Jazyk angličtina Země Spojené státy americké Médium print

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40755376

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

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.

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

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...