Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences

Authors

  • Erika Tóth National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest https://orcid.org/0000-0003-2054-8447
  • Zsófia Kürönya National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology https://orcid.org/0000-0001-8500-5924
  • Edina Soós National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology
  • Tamás Pintér National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology https://orcid.org/0000-0001-7462-9424
  • Henriett Butz National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Genetics, National Institute of Oncology; HUN-REN Hereditary Cancer Research Group, Budapest, Hungary; Central Biobank, National Institute of Oncology, Budapest https://orcid.org/0000-0003-1664-409X
  • Zsolt Horváth National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology https://orcid.org/0000-0002-5376-7737
  • Erzsébet Csernák National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
  • Vince Kornél Grolmusz National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Genetics, National Institute of Oncology; HUN-REN Hereditary Cancer Research Group, Budapest, Hungary https://orcid.org/0000-0002-5677-895X
  • Judit Székely National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary
  • Tamás Straussz National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
  • József Lövey National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary https://orcid.org/0000-0001-6467-191X
  • Levenete Jánvári National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary
  • László Báthory-Fülöp National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
  • Péter Nagy National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary https://orcid.org/0000-0003-3393-235X
  • Csaba Polgár National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary https://orcid.org/0000-0001-7245-0762
  • Attila Patócs National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Genetics, National Institute of Oncology; HUN-REN Hereditary Cancer Research Group, Budapest, Hungary https://orcid.org/0000-0001-7506-674X

DOI:

https://doi.org/10.2340/1651-226X.2024.39918

Keywords:

Tumour mutation profile, molecular tumour board, targeted therapy

Abstract

Recent developments in molecular genetic testing methods (e.g. next-generation sequencing [NGS]-panels) largely accelerated the process of finding the most appropriate targeted therapeutic intervention for cancer patients based on molecularly targetable genetic alterations. In Hungary, a centralized approval system following the recommendation of the National Molecular Tumor Board was launched for the coordination of all aspects of comprehensive genetic profiling (CGP) including patient selection and therapy reimbursement.

Aim: The study aims to evaluate the clinical benefit of CGP in our Comprehensive Cancer Center

Methods and patients: CGP was introduced into our routine clinical practice in 2021. An NGS-based large (> 500 genes) gene panel was used for cases where molecular genetic testing was approved by the National Molecular Tumor Board. From 2021 until August 2023 163 cases were tested. The majority of them were ECOG 0–1 patients with advanced-stage diseases, histologically rare cancer, or cancers with unknown primary tumours.

Results: Seventy-four cases (74 of 163, 45%) had clinically relevant genetic alterations. In 34 patients, the identified variants represented an indication for an approved therapy (approved by the Hungarian authorities, on-label indication), while in 40 cases the recommended therapy did not have an approved indication in Hungary for certain tumour types, but off-label indication could be recommended. Based on our CGP results, 24 patients (24/163; 14.7%) received targeted therapy. Treatment duration was between 1 and 60 months. In total 14 (14/163; 8.5% of the tested cases) patients had a positive clinical response (objective response or stable disease) and were treated for more than 16 weeks.

Interpretation: NGS-based CGP was successfully introduced in our institution and a significant number of patients benefited from comprehensive genetic tests. Our preliminary results can serve as the starting point of Drug Rediscovery Protocol (DRUP) studies.

Downloads

Download data is not yet available.

References

Svoboda M, Lohajova Behulova R, Slamka T, Sebest L, Repiska V. Comprehensive genomic profiling in predictive testing of cancer. Physiol Res. 2023;72:S267–75.

https://doi.org/10.33549/physiolres.935154 DOI: https://doi.org/10.33549/physiolres.935154

Malone ER, Oliva M, Sabatini PJB, Stockley TL, Siu LL. Molecular profiling for precision cancer therapies. Genome Med. 2020;12:8.

https://doi.org/10.1186/s13073-019-0703-1 DOI: https://doi.org/10.1186/s13073-019-0703-1

Chawla A, Janku F, Wheler JJ, Miller VA, Ryan J, Anhorn R, et al. Estimated cost of anticancer therapy directed by comprehensive genomic profiling in a single-center study. JCO Precis Oncol. 2018;2:1–11.

https://doi.org/10.1200/PO.18.00074 DOI: https://doi.org/10.1200/PO.18.00074

Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31:1491–505.

https://doi.org/10.1016/j.annonc.2020.07.014 DOI: https://doi.org/10.1016/j.annonc.2020.07.014

van Waalwijk van Doorn-Khosrovani SB, Pisters-van Roy A, van Saase L, van der Graaff M, Gijzen J, Sleijfer S, et al. Personalised reimbursement: a risk-sharing model for biomarker-driven treatment of rare subgroups of cancer patients. Ann Oncol. 2019;30:663–5.

https://doi.org/10.1093/annonc/mdz119 DOI: https://doi.org/10.1093/annonc/mdz119

Tsimberidou AM, Kahle M, Vo HH, Baysal MA, Johnson A, Meric-Bernstam F. Molecular tumour boards – current and future considerations for precision oncology. Nat Rev Clin Oncol. 2023;20:843–63.

https://doi.org/10.1038/s41571-023-00824-4 DOI: https://doi.org/10.1038/s41571-023-00824-4

Taskén K, Russnes HEG, Aas E, Bjørge L, Blix ES, CONNECT Public–Private Partnership Consortium, et al. A national precision cancer medicine implementation initiative for Norway. Nat Med. 2022;28:885–87.

https://doi.org/10.1038/s41591-022-01777-4 DOI: https://doi.org/10.1038/s41591-022-01777-4

Larson KL, Huang B, Weiss HL, Hull P, Westgate PM, Miller RW, et al. Clinical outcomes of molecular tumor boards: a systematic review. JCO Precis Oncol. 2021;5:1122–32.

https://doi.org/10.1200/PO.20.00495 DOI: https://doi.org/10.1200/PO.20.00495

Kikuchi J, Ohhara Y, Takada K, Tanabe H, Hatanaka K, Amano T. Clinical significance of comprehensive genomic profiling tests covered by public insurance in patients with advanced solid cancers in Hokkaido, Japan. Jpn J Clin Oncol. 2021;51:753–61.

https://doi.org/10.1093/jjco/hyaa277 DOI: https://doi.org/10.1093/jjco/hyaa277

Kondo T, Matsubara J, Quy PN, Fukuyama K, Nomura M, Funakoshi T, et al. Comprehensive genomic profiling for patients with chemotherapy‐naïve advanced cancer. Cancer Sci. 2021;112:296–304.

https://doi.org/10.1111/cas.14674 DOI: https://doi.org/10.1111/cas.14674

Shirota H, Komine K, Takahashi M, Takahashi S, Miyauchi E, Niizuma H, et al. Clinical decisions by the molecular tumor board on comprehensive genomic profiling tests in Japan: a retrospective observational study. Cancer Med. 2023;12:6170–81.

https://doi.org/10.1002/cam4.5349 DOI: https://doi.org/10.1002/cam4.5349

van der Velden DL, Hoes LR, van der Wijngaart H, van Berge Henegouwen JM, van Werkhoven E, Roepman P, et al. The Drug Rediscovery protocol facilitates the expanded use of existing anticancer drugs. Nature. 2019;574:127–131.

https://doi.org/10.1038/s41586-019-1600-x DOI: https://doi.org/10.1038/s41586-019-1600-x

Helland Å, Russnes HG, Fagereng GL, Al-Shibli K, Andersson Y, Berg T, et al. Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway. J Transl Med. 2022;20:225. DOI: https://doi.org/10.1016/j.annonc.2022.07.631

https://doi.org/10.1186/s12967-022-03432-5 DOI: https://doi.org/10.1186/s12967-022-03432-5

Kringelbach T, Højgaard M, Rohrberg K, Spanggaard I, Laursen BE, Ladekarl M. ProTarget: A Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling – a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial. BMC Cancer. 2023;23:182.

https://doi.org/10.1186/s12885-023-10632-9 DOI: https://doi.org/10.1186/s12885-023-10632-9

Published

2024-06-16

How to Cite

Tóth, E., Kürönya, Z., Soós, E., Pintér, T., Butz, H., Horváth, Z., … Patócs, A. (2024). Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences. Acta Oncologica, 63(1), 433–440. https://doi.org/10.2340/1651-226X.2024.39918