medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-22-154-159medsovet-7253Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONКлинический случай длительного контроля над заболеванием у пациентки с EGFR-позитивным немелкоклеточным раком легкогоClinical case of long-term disease control in a patient with EGFR-positive non-small cell lung cancerhttps://orcid.org/0000-0003-0181-2919КузьминаВ. А.KuzminaV. A.

Кузьмина Валерия Александровна - ординатор отделения лекарственных методов лечения (химиотерапевтическое) №17.

115478, Москва, Каширское шоссе, д. 24

Valeriya A. Kuzmina - Resident, Cancer Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478

emerallld@yandex.ruhttps://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovK. K.

Лактионов Константин Константинович – доктор медицинских наук, заведующий онкологическим отделением лекарственных методов лечения (химиотерапевтическое) №17, НМИЦ онкологии им. Н.Н. Блохина; профессор кафедры онкологии и лучевой терапии лечебного факультета, РНИМУ им. Н.И. Пирогова.

115478, Москва, Каширское шоссе, д. 24; 117997, Москва, ул. Островитянова, д. 1

Konstantin K. Laktionov - Dr. Sci. (Med.), Head of Cancer Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology; Professor, Department of Oncology and X-ray Therapy, General Medicine Faculty, Pirogov Russian National Research Medical University.

24, Kashirskoye Shosse, Moscow, 115478; 1, Ostrovityanov St., Moscow, 117997

lkoskos@mail.ruhttps://orcid.org/0000-0002-2154-3376РеутоваЕ. В.ReutovaE. V.

Реутова Елена Валерьевна – кандидат медицинских наук, старший научный сотрудник отделения лекарственных методов лечения (химиотерапевтическое) №17.

115478, Москва, Каширское шоссе, д. 24

Elena V. Reutova - Cand. Sci. (Med.), Senior Research Associate of Cancer Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478

ereutova@rambler.ruhttps://orcid.org/0000-0002-8967-7987АрдзинбаМ. С.ArdzinbaM. A.

Ардзинба Мераб Сергеевич - кандидат медицинских наук, научный сотрудник отделения лекарственных методов лечения (химиотерапевтическое) №17.

115478, Москва, Каширское шоссе, д. 24

Merab A. Ardzinba - Cand. Sci. (Med.), Research Associate of Cancer Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478

merabii@mail.ruhttps://orcid.org/0000-0002-3710-137XДенисоваЕ. С.DenisovaE. S.

Денисова Елена Сергеевна - аспирант отделения лекарственных методов лечения (химиотерапевтическое) №17.

115478, Москва, Каширское шоссе, д. 24

Elena S. Denisova - Postgraduate Student, Cancer Drug Therapy (Chemotherapeutic) Department No. 17, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478

denielena95@yandex.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияBlokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical UniversityRussian Federation202207122022022154159Copyright © Кузьмина В.А., Лактионов К.К., Реутова Е.В., Ардзинба М.С., Денисова Е.С., 20222022Кузьмина В.А., Лактионов К.К., Реутова Е.В., Ардзинба М.С., Денисова Е.С.Kuzmina V.A., Laktionov K.K., Reutova E.V., Ardzinba M.A., Denisova E.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7253

Рак легкого остается ведущей причиной смерти от злокачественных новообразований как в России, так и во всем мире, часто диагностируется на поздних стадиях заболевания, а медиана выживаемости при применении стандартной химиотерапии на основе препаратов платины, как правило, не превышает одного года. Открытие активирующих мутаций рецептора эпидермального фактора роста (EGFR) стало отправной точкой в персонализированном лечении распространенного немелкоклеточного рака легкого и привело к изменению терапевтических подходов и улучшению прогноза у тщательно отобранной категории пациентов. В настоящее время проведение молекулярно-генетического исследования на поздних стадиях заболевания вошло в рутинную практику, применение таргетных препаратов стало стандартом 1-й линии терапии, а тактика лечения при прогрессировании заболевания может основываться не только на рентгенологических критериях RECIST, но и на динамике клинических проявлений и определении возможного механизма резистентности. Представленный клинический случай демонстрирует возможность длительного контроля над заболеванием при сохранении удовлетворительного качества жизни на фоне применения таргетной терапии, особенности оценки эффективности проводимого лечения, а также преимущества стратегии продолженной терапии при бессимптомном прогрессировании заболевания.

Lung cancer remains the leading cause of cancer-related deaths both in Russia and worldwide, it is often diagnosed at a late stage and the median survival with traditional first-line chemotherapy platinum-based regimens does not exceed one year. The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene offered first opportunity for personalized treatment of advanced non-small cell lung cancer. Currently, molecular testing for patients with advanced-stage lung adenocarcinoma is a routine activity, the use of targeted agents has become the standard of the 1st line of therapy, the treatment strategy after disease progression based not only on the RECIST radiological criteria, but also on the dynamics of clinical symptoms and the identification of a possible mechanism of resistance. The clinical case below demonstrates safe and long-term control of the disease in patient receiving target agents treatment, features of evaluation the effectiveness of the treatment, and also illustrates the advantages of the strategy of continued therapy with asymptomatic progression of the disease.

немелкоклеточный рак легкогомутация EGFRтаргетная терапиягефитинибосимертиниббессимптомное прогрессирование заболеванияnon-small cell lung cancerEGFR mutationtarget therapygefitinibosimertinibasymptomatic disease progressionReferencesSung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. https://doi.org/10.3322/caac.21660.Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. https://doi.org/10.3322/caac.21660.Schiller J.H., Harrington D., Belani C.P., Langer C., Sandler A., Krook J. et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-98. https://doi.org/10.1056/NEJMoa011954.Schiller J.H., Harrington D., Belani C.P., Langer C., Sandler A., Krook J. et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-98. https://doi.org/10.1056/NEJMoa011954.Mazza V., Cappuzzo F. Treating EGFR mutation resistance in non-small cell lung cancer - role of osimertinib. Appl Clin Genet. 2017;10:49-56. https://doi.org/10.2147/TACG.S103471.Mazza V., Cappuzzo F. Treating EGFR mutation resistance in non-small cell lung cancer - role of osimertinib. Appl Clin Genet. 2017;10:49-56. https://doi.org/10.2147/TACG.S103471.Lynch T.J., Bell D.W., Sordella R., Gurubhagavatula S., Okimoto R.A., Brannigan B.W. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. https://doi.org/10.1056/NEJMoa040938.Lynch T.J., Bell D.W., Sordella R., Gurubhagavatula S., Okimoto R.A., Brannigan B.W. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. https://doi.org/10.1056/NEJMoa040938.Westover D., Zugazagoitia J., Cho B.C., Lovly C.M., Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 2018;29(Suppl. 1):i10-i19. https://doi.org/10.1093/annonc/mdx703.Westover D., Zugazagoitia J., Cho B.C., Lovly C.M., Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 2018;29(Suppl. 1):i10-i19. https://doi.org/10.1093/annonc/mdx703.Thongprasert S., Duffield E., Saijo N., Wu Y.L., Yang J.C., Chu D.T. et al. Health-related quality-of-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS). J Thorac Oncol. 2011;6(11):1872-1880. https://doi.org/10.1097/JTO.0b013e31822adaf7.Thongprasert S., Duffield E., Saijo N., Wu Y.L., Yang J.C., Chu D.T. et al. Health-related quality-of-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS). J Thorac Oncol. 2011;6(11):1872-1880. https://doi.org/10.1097/JTO.0b013e31822adaf7.Chen G., Feng J., Zhou C., Wu Y.L., Liu X.Q., Wang C. et al. Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol. 2013;24(6):1615-1622. https://doi.org/10.1093/annonc/mdt012.Chen G., Feng J., Zhou C., Wu Y.L., Liu X.Q., Wang C. et al. Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol. 2013;24(6):1615-1622. https://doi.org/10.1093/annonc/mdt012.Mok T.S., Wu Y.L., Thongprasert S., Yang C.H., Chu D.T., Saijo N. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-957. https://doi.org/10.1056/NEJMoa0810699.Mok T.S., Wu Y.L., Thongprasert S., Yang C.H., Chu D.T., Saijo N. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-957. https://doi.org/10.1056/NEJMoa0810699.Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239-246. https://doi.org/10.1016/S1470-2045(11)70393-X.Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239-246. https://doi.org/10.1016/S1470-2045(11)70393-X.Kobayashi S., Boggon TJ., Dayaram T., Janne P.A., Kocher O., Meyerson M. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefi-tinib. N Engl J Med. 2005;352(8):786-792. https://doi.org/10.1056/NEJMoa044238.Kobayashi S., Boggon TJ., Dayaram T., Janne P.A., Kocher O., Meyerson M. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefi-tinib. N Engl J Med. 2005;352(8):786-792. https://doi.org/10.1056/NEJMoa044238.Pao W., Miller V.A., Politi K.A., Riely G.J., Somwar R., Zakowski M.F. et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005;2(3):e73. https://doi.org/10.1371/journal.pmed.0020073.Pao W., Miller V.A., Politi K.A., Riely G.J., Somwar R., Zakowski M.F. et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005;2(3):e73. https://doi.org/10.1371/journal.pmed.0020073.Lee J.W., Soung Y.H., Kim S.Y., Nam S.W., Park W.S., Wang Y.P. et al. ERBB2 kinase domain mutation in the lung squamous cell carcinoma. Cancer Lett. 2006;237(1):89-94. https://doi.org/10.1016/j.canlet.2005.05.026.Lee J.W., Soung Y.H., Kim S.Y., Nam S.W., Park W.S., Wang Y.P. et al. ERBB2 kinase domain mutation in the lung squamous cell carcinoma. Cancer Lett. 2006;237(1):89-94. https://doi.org/10.1016/j.canlet.2005.05.026.Miller V.A., Hirsh V., Cadranel J., Chen Y.M., Park K., Kim S.W. et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012;13(5):528-538. https://doi.org/10.1016/S1470-2045(12)70087-6.Miller V.A., Hirsh V., Cadranel J., Chen Y.M., Park K., Kim S.W. et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012;13(5):528-538. https://doi.org/10.1016/S1470-2045(12)70087-6.Mok T.S., Wu Y.L., Ahn M.J., Garassino M.C., Kim H.R., Ramalingam S.S. et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017;376(7):629-640. https://doi.org/10.1056/NEJMoa1612674.Mok T.S., Wu Y.L., Ahn M.J., Garassino M.C., Kim H.R., Ramalingam S.S. et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017;376(7):629-640. https://doi.org/10.1056/NEJMoa1612674.Soria J.C., Ohe Y., Vansteenkiste J., Reungwetwattana T., Chewaskulyong B., Lee K.H. et al. Osimertinib in Untreated EGFR-Mutated Advanced NonSmall-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. https://doi.org/10.1056/NEJMoa1713137.Soria J.C., Ohe Y., Vansteenkiste J., Reungwetwattana T., Chewaskulyong B., Lee K.H. et al. Osimertinib in Untreated EGFR-Mutated Advanced NonSmall-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. https://doi.org/10.1056/NEJMoa1713137.Ramalingam S.S., Vansteenkiste J., Planchard D., Cho B.C., Gray J.E., Ohe Y. et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020;382(1):41-50. https://doi.org/10.1056/NEJMoa1913662.Ramalingam S.S., Vansteenkiste J., Planchard D., Cho B.C., Gray J.E., Ohe Y. et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020;382(1):41-50. https://doi.org/10.1056/NEJMoa1913662.Goto Y., Tanai C., Yoh K., Hosomi Y., Sakai H., Kato T. et al. Continuing EGFR-TKI beyond radiological progression in patients with advanced or recurrent, EGFR mutation-positive non-small-cell lung cancer: an observational study. ESMO Open. 2017;2(4):e000214. https://doi.org/10.1136/esmoopen-2017-000214.Goto Y., Tanai C., Yoh K., Hosomi Y., Sakai H., Kato T. et al. Continuing EGFR-TKI beyond radiological progression in patients with advanced or recurrent, EGFR mutation-positive non-small-cell lung cancer: an observational study. ESMO Open. 2017;2(4):e000214. https://doi.org/10.1136/esmoopen-2017-000214.Papadimitrakopoulou V.A., Mok T.S., Han J.Y., Ahn M.J., Delmonte A., Ramalingam S.S. et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020;31(11):1536-1544. https://doi.org/10.1016/j.annonc.2020.08.21001.Papadimitrakopoulou V.A., Mok T.S., Han J.Y., Ahn M.J., Delmonte A., Ramalingam S.S. et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020;31(11):1536-1544. https://doi.org/10.1016/j.annonc.2020.08.21001.

The authors declare that there are no conflicts of interest present.