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Resolution on the results of Advisory Board “Searching the effective methods of testing and treating patients with NSCLC caused by NTRK gene fusions“

https://doi.org/10.21518/2079-701X-2022-16-9-50-56

Abstract

The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months.

About the Authors

E. V. Artamonova
Blokhin National Medical Research Center of Oncology
Russian Federation

Elena V. Artamonova - Dr. Sci. (Med.), Professor, Head of Drug Therapy (Chemotherapeutic) Department No. 1, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.



V. V. Breder
Blokhin National Medical Research Center of Oncology
Russian Federation

Valeriy V. Breder - Dr. Sci. (Med.), Lead Research Associate, Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.



L. Yu. Vladimirova
National Medical Research Centre for Oncology
Russian Federation

Lubov Yu. Vladimirova - Dr. Sci. (Med.), Professor, Head of Department of Cancer Drug Therapy No. 1, National Medical Research Centre for Oncology.

63, 14th Liniya St., Rostov-on-Don, 344037.



I. A. Demidova
Moscow City Oncology Hospital No. 62
Russian Federation

Irina А. Demidova - Cand. Sci. (Biol.), Head of Molecular Biological Laboratory, Moscow City Oncology Hospital No. 62.

6, Staropetrovskiy Proezd, Moscow, 125130



E. N. Imyanitov
Petrov National Medical Cancer Research Centre
Russian Federation

Evgeny N. Imyanitov - Corr. Member RAS, Dr. Sci. (Med.), Professor, Head of Reference Center, Head of Tumour Growth Biology Department, Petrov National Medical Cancer Research Centre.

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758.



К. К. Laktionov
Blokhin National Medical Research Center of Oncology
Russian Federation

Konstantin К. Laktionov - Dr. Sci. (Med.), Professor, Head of Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478.



M. P. Matrosova
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation

Marina P. Matrosova - Head of Hospital Chemotherapeutic Service 2, Nizhny Novgorod Regional Clinical Oncology Dispensary.

11/1, Delovaya St., Nizhny Novgorod, 603126.



S. V. Orlov
Pavlov First Saint Petersburg State Medical University
Russian Federation

Sergey V. Orlov - Corr. Member RAS, Dr. Sci. (Med.), Professor, Leading Research Associate, Department of Clinical Oncology, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University.

6-8, Lev Tolstoy St., St Petersburg, 197022.



E. О. Rodionov
Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University
Russian Federation

Еvgeny О. Rodionov - Cand. Sci. (Med.), Leading Research Associate, Department of Thoracic Oncology, Research Institute of Oncology, Tomsk National Research Medical Center of the Russian Academy of Sciences; Teaching Assistant, Department of Oncology, Siberian State Medical University.

5, Kooperativnyy Lane, Tomsk, 634009; 2, Moskovskiy Trakt, Tomsk, 634050.



D. D. Sakaeva
Clinical Hospital “Mother and Child”
Russian Federation

Dina D. Sakaeva - Dr. Sci. (Med.), Professor, Deputy Chief Physician for Oncology, Clinical Hospital “Mother and Child”.

137, Bldg. 2, Starokubanskaya St., Krasnodar, 350075.



M. I. Sekacheva
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Marina I. Sekacheva - Dr. Sci. (Med.), Professor, Director of Institute of Personalized Medicine, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991.



A. V. Smolin
Main Military Clinical Hospital named after Academician N.N. Burdenko
Russian Federation

Alexey V. Smolin - Cand. Sci. (Med.), Head of Radiological Center, Main Military Clinical Hospital named after Academician N.N. Burdenko.

3, Gospital'naya Square, Moscow, 105094.



N. V. Fadeeva
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation

Natalya V. Fadeeva - Cand. Sci. (Med.), Head of Oncological Department of Anti-tumour Drug Therapy (Chemotherapy), Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine.

42, Blyukher St., Chelyabinsk, 454087.



M. L. Filipenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Maxim L. Filipenko - Cand. Sci. (Biol.), Head of Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences.

8, Akademik Lavrent'ev Ave., Novosibirsk, 630090.



References

1. Cocco E., Scaltriti M., Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731-747. https://doi.org/10.1038/s41571-018-0113-0.

2. Vaishnavi A., Le A.T., Doebele R.C. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34. https://doi.org/10.1158/2159-8290.CD-14-0765.

3. Amatu A., Sartore-Bianchi A., Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023. https://doi.org/10.1136/esmoopen-2015-000023.

4. Khotskaya Y.B., Holla V.R., Farago A.F., Shaw K.R.M., Meric-Bernstam F., Hong D.S. Targeting TRK family proteins in cancer. Pharmacol Ther. 2017;173:58-66. https://doi.org/10.1016/j.pharmthera.2017.02.006.

5. Brodeur G.M., Minturn J.E., Ho R., Simpson A.M., Iyer R., Varela C.R. et al. Trk receptor expression and inhibition in neuroblastomas. Clin Cancer Res. 2009;15(10):3244-3250. https://doi.org/10.1158/1078-0432.CCR-08-1815.

6. Reichardt L.F. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006;361(1473):1545-1564. https://doi.org/10.1098/rstb.2006.1894.

7. Valent A., Danglot G., Bernheim A. Mapping of the tyrosine kinase receptors trkA (NTRK1), trkB (NTRK2) and trkC (NTRK3) to human chromosomes 1q22, 9q22 and 15q25 by fluorescence in situ hybridization. Eur J Hum Genet. 1997;5(2):102-104. Available at: https://pubmed.ncbi.nlm.nih. gov/9195161/.

8. Pirker R., Herth F.J., Kerr K.M., Filipits M., Taron M., Gandara D. et al. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop. J Thor Oncol. 2010;5(10):1706-1713. https://doi.org/10.1097/JTO.0b013e3181f1c8de.

9. Kim S., Park C., Ji Y., Kim D.G., Bae H., van Vrancken M. et al. Deamination Effects in Formalin-Fixed, Paraffin-Embedded Tissue Samples in the Era of Precision Medicine. J Mol Diagn. 2017;19(1):137-146. https://doi.org/10.1016/j.jmoldx.2016.09.006.

10. Dumenil C., Massiani M.-A., Dumoulin J., Giraud V., Labrune S., Chinet T., Leprieur E.G. Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab. PLoS ONE. 2018;13(4):e0195945. https://doi.org/10.1371/journal.pone.0195945.

11. Costantini A., Corny J., Fallet V., Renet S., Friard S., Chouaid C. et al. Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer. ERJ Open Research. 2018;4(2):00120-2017. https://doi.org/10.1183/23120541.00120-2017.

12. Gatalica Z., Xiu J., Swensen J., Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. https://doi.org/10.1038/s41379-018-0118-3.

13. Farago A.F., Taylor M.S., Doebele R.C., Zhu V.W., Kummar S., Spira A.I. et al. Clinicopathologic Features of Non-Small-Cell Lung Cancer Harboring an NTRK Gene Fusion. JCO Precis Oncol. 2018;2018:PO.18.00037. https://doi.org/10.1200/PO.18.00037.

14. Drilon A., Laetsch T.W., Kummar S., DuBois S.G., Lassen U.N., Demetri G.D. et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739. https://doi.org/10.1056/NEJMoa1714448.

15. Hong D.S., Shen L., van Tilburg C.M., Tan D.S.-W., Kummar S., Lin J.J. et al. Longterm efficacy and safety of larotrectinib in an integrated dataset of patients with TRK fusion cancer. J Clin Oncol. 2021;39(15_suppl):3108-3108. https://doi.org/10.1200/JCO.2021.39.15_suppl.3108.

16. Hong D.S., DuBois S.G., Kummar S., Farago A., Albert C.M., Rohrberg K.S. et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2021;21(4):531-540. https://doi.org/10.1016/S1470-2045(19)30856-3.

17. Laetsch T.W., DuBois S.G., Mascarenhas L., Turpin B., Federman N., Albert C.M. et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018;19(5):705-714. https://doi.org/10.1016/S1470-2045(18)30119-0.

18. Hyman D.M., Laetsch T.W., Kummar S., DuBois S.G., Farago A.F., Pappo A.S. et al. The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers. J Clin Oncol. 2017;35(18_suppl). https://doi.org/10.1200/jco.2017.35.18_suppl.lba2501.

19. Hyman D.M., van Tilburg C.M., Albert C.M., Tan D.S.W., Geoerger B., Farago A.F. et al. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Ann Oncol. 2019;30(5):v162-v163. https://doi.org/10.1093/annonc/mdz244.007.

20. McDermott R., van Tilburg C.M., Farago A.F., Kummar S., Tan D.S.W., Albert C.M. et al. Survival benefits of larotrectinib in an integrated dataset of patients with TRK fusion cancer. Ann Oncol. 2020;31(4 Suppl.):S1101-S1102. https://doi.org/10.1016/j.annonc.2020.08.1347.

21. Mascarenhas L., Albert C., Pappo A., Geoerger B., Doz F., Federman N. et al. Larotrectinib Demonstrates Durable Efficacy and Safety in an Expanded Dataset Of Pediatric Patients With TRK Fusion Cancer. Ped Blood Canc. 2020;67(S4). https://doi.org/10.1002/pbc.28742.


Review

For citations:


Artamonova EV, Breder VV, Vladimirova LY, Demidova IA, Imyanitov EN, Laktionov КК, Matrosova MP, Orlov SV, Rodionov EО, Sakaeva DD, Sekacheva MI, Smolin AV, Fadeeva NV, Filipenko ML. Resolution on the results of Advisory Board “Searching the effective methods of testing and treating patients with NSCLC caused by NTRK gene fusions“. Meditsinskiy sovet = Medical Council. 2022;(9):50-56. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-9-50-56

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ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)