medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2019-19-126-131medsovet-5288Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONВозможности таргетной терапии метастатического колоректального рака с гиперэкспрессией HER2: клинический случайPossibilities of therapeutic use of HER2-inhibitorsin metastatic colorectal cancer: a case reporthttps://orcid.org/0000-0001-5530-3234КачмазовА. А.KachmazovA. A.

младший научный сотрудник отдела лекарственного лечения опухолей

125284, Россия, Москва, 2-й Боткинский проезд, д. 3

SPIN-код: 7547-7725; AuthorID: 1041704

Junior Researcher, Department of Antitumor Drug Therapy

3, 2-nd Botkinskiy proezd, Moscow, 125284, Russia

SPIN-code: 7547-7725; AuthorID: 1041704

andrewkachmazov@gmail.comhttps://orcid.org/0000-0003-4879-2687БолотинаЛ. В.BolotinaL. V.

д.м.н., заведующая отделением химиотерапии отдела лекарственного лечения опухолей,

125284, Россия, Москва, 2-й Боткинский проезд, д. 3

SPIN-код: 2787-5414; AuthorID: 594953

Dr. of Sci. (Med.), Head of Chemotherapy Unit, Department of Antitumor Drug Therapy

 3, 2-nd Botkinskiy proezd, Moscow, 125284, Russia

SPIN-code: 2787-5414; AuthorID: 594953

lbolotina@yandex.ruhttps://orcid.org/0000-0003-0092-0459КорниецкаяА. Л.KornietskayaA. L.

к.м.н., старший научный сотрудник отделения химиотерапии отдела лекарственного лечения опухолей

SPIN-код: 2651-7158; AuthorID: 951395

125284, Россия, Москва, 2-й Боткинский проезд, д. 3

Cand. of Sci. (Med.), Senior Researcher, Chemotherapy Unit, Department of Antitumor Drug Therapy

3, 2-nd Botkinskiy proezd, Moscow, 125284, Russia

SPIN-code: 2651-7158; AuthorID: 951395

kornietskaya@mail.ruhttps://orcid.org/0000-0002-2061-0522УстиноваТ. В.UstinovaT. V.

врач отделения химиотерапии отдела лекарственного лечения опухолей

SPIN-код: 3638-0120; AuthorID: 951518

125284, Россия, Москва, 2-й Боткинский проезд, д. 3

Dr. of Sci. (Med.), Physician of Chemotherapy Unit, Department of Antitumor Drug Therapy

3, 2-nd Botkinskiy proezd, Moscow, 125284, Russia

SPIN-code: 3638-0120; AuthorID: 951518

t.v.rafeyenko@gmail.comhttps://orcid.org/0000-0001-6917-6520ТолстовВ. А.TolstovV. A.

врач-ординатор отделения химиотерапии отдела лекарственного лечения опухолей

125284, Россия, Москва, 2-й Боткинский проезд, д. 3

Dr. of Sci. (Med.), Resident Physician of Chemotherapy Unit, Department of Antitumor Drug Therapy

3, 2-nd Botkinskiy proezd, Moscow, 125284, Russia

vlatolstov@gmail.comФеденкоА. А.FedenkoA. A.

д.м.н., руководитель отдела лекарственного лечения опухолей

SPIN-код: 9847-7668; AuthorID: 823233  ORCID: 0000-0353-4472-5600

125284, Россия, Москва, 2-й Боткинский проезд, д. 3

Dr. of Sci. (Med.), Head of Department of Antitumor Drug Therapy

3, 2-nd Botkinskiy proezd, Moscow, 125284, Russia

SPIN-code: 9847-7668; AuthorID: 823233

fedenko@eesg.ruНациональный медицинский исследовательский центр радиологииРоссияFederal State Budgetary Institution «National Medical Research Radiological Center» of the Ministry of Health of the Russian FederationRussian Federation201906122019019126131Copyright © Качмазов А.А., Болотина Л.В., Корниецкая А.Л., Устинова Т.В., Толстов В.А., Феденко А.А., 20192019Качмазов А.А., Болотина Л.В., Корниецкая А.Л., Устинова Т.В., Толстов В.А., Феденко А.А.Kachmazov A.A., Bolotina L.V., Kornietskaya A.L., Ustinova T.V., Tolstov V.A., Fedenko A.A.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/5288химиотерапиятаргетная терапиятрастузумабколоректальный ракHER2chemotherapytargeted therapyHER2trastuzumabcolorectal cancerReferencesКаприн А.Д., Старинский В.В. Злокачественные новообразования в России в 2017 году (заболеваемость и смертность). P. 250. Режим доступа: http://www.oncology.ru/service/statistics/malignant_tumors/2017.pdfKaprin A.D., Starinskiy V.V. Malignant neoplasms in Russian Federation in 2017 (incidence and mortality). P. 250 (In Russ.) Available at: http://www.oncology.ru/service/statistics/malignant_tumors/2017.pdf.Rakha E.A. et al. Updated UK Recommendations for HER2 assessment in breast cancer. Journal of Clinical Pathology. 2015;68(2):93–99. doi: 10.1136/jclinpath-2014-202571.Rakha E.A. et al. Updated UK Recommendations for HER2 assessment in breast cancer. Journal of Clinical Pathology. 2015;68(2):93–99. doi: 10.1136/jclinpath-2014-202571.Rüschoff J. et al. HER2 testing in gastric cancer: a practical approach. Modern Pathology. 2012;25(5):637–650. Available at: https://www.nature.com/articles/modpathol2011198.Rüschoff J. et al. HER2 testing in gastric cancer: a practical approach. Modern Pathology. 2012;25(5):637–650. Available at: https://www.nature.com/articles/modpathol2011198.Kim E.K. et al. The frequency and clinical impact of HER2 alterations in lung adenocarcinoma. PLoS ONE. 2017;12(2):e0171280. doi: 10.1371/journal.pone.0171280.Kim E.K. et al. The frequency and clinical impact of HER2 alterations in lung adenocarcinoma. PLoS ONE. 2017;12(2):e0171280. doi: 10.1371/journal.pone.0171280.Schwartz R.S., Erban J.K. Timing of Metastasis in Breast Cancer. New England Journal of Medicine. 2017;376(25):2486–2488. doi: 10.1056/NEJMcibr1701388.Schwartz R.S., Erban J.K. Timing of Metastasis in Breast Cancer. New England Journal of Medicine. 2017;376(25):2486–2488. doi: 10.1056/NEJMcibr1701388.Liang J. et al. Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature. Tumor Biol. 2014;35(5):4849–4858. Available at: https://link.springer.com/article/10.1007%2Fs13277-014-1636-3.Liang J. et al. Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature. Tumor Biol. 2014;35(5):4849–4858. Available at: https://link.springer.com/article/10.1007%2Fs13277-014-1636-3.Ettl T. et al. Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer. British Journal of Cancer. 2012;106(4):719–726. Available at: https://www.nature.com/articles/bjc2011605.Ettl T. et al. Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer. British Journal of Cancer. 2012;106(4):719–726. Available at: https://www.nature.com/articles/bjc2011605.McKay J.A. et al. c-erb B-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002;86(4):568–573. Available at: https://www.nature.com/articles/6600127.McKay J.A. et al. c-erb B-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002;86(4):568–573. Available at: https://www.nature.com/articles/6600127.Song Z. et al. Immunohistochemical results of HER2/neu protein expression assessed by rabbit monoclonal antibodies SP3 and 4B5 in colorectal carcinomas. Int J Clin Exp Pathol. 2014;7(7):4454–4460. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25120833/Song Z. et al. Immunohistochemical results of HER2/neu protein expression assessed by rabbit monoclonal antibodies SP3 and 4B5 in colorectal carcinomas. Int J Clin Exp Pathol. 2014;7(7):4454–4460. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25120833/Bufill J.A. Colorectal Cancer: Evidence for Distinct Genetic Categories Based on Proximal or Distal Tumor Location. Ann Intern Med. 1990;113(10):779. doi: 10.7326/0003-4819-113-10-779.Bufill J.A. Colorectal Cancer: Evidence for Distinct Genetic Categories Based on Proximal or Distal Tumor Location. Ann Intern Med. 1990;113(10):779. doi: 10.7326/0003-4819-113-10-779.Marshall J. et al. Molecular variances between rectal and left-sided colon cancers. JCO. 2017;35(4_suppl.):522–522. doi: 10.1200/JCO.2017.35.4_suppl.522.Marshall J. et al. Molecular variances between rectal and left-sided colon cancers. JCO. 2017;35(4_suppl.):522–522. doi: 10.1200/JCO.2017.35.4_suppl.522.Bertotti A. et al. A Molecularly Annotated Platform of Patient-Derived Xenografts («Xenopatients») Identifies HER2 as an Effective Therapeutic Target in CetuximabResistant Colorectal Cancer. Cancer Discov. 2011;1(6):508–523. doi: 10.1158/2159-8290.CD-11-0109.Bertotti A. et al. A Molecularly Annotated Platform of Patient-Derived Xenografts («Xenopatients») Identifies HER2 as an Effective Therapeutic Target in CetuximabResistant Colorectal Cancer. Cancer Discov. 2011;1(6):508–523. doi: 10.1158/2159-8290.CD-11-0109.Richman S.D. et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. The Journal of Pathology. 2016;238(4):562–570. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/path.4679.Richman S.D. et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. The Journal of Pathology. 2016;238(4):562–570. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/path.4679.Valtorta E. et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol. 2015;28(11):1481–1491. doi: 10.1038/modpathol.2015.98.Valtorta E. et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol. 2015;28(11):1481–1491. doi: 10.1038/modpathol.2015.98.Conradi L.-C. et al. Frequency of HER-2 Positivity in Rectal Cancer and Prognosis. The American Journal of Surgical Pathology. 2013;37(4):522. doi: 10.1097/PAS.0b013e318272ff4d.Conradi L.-C. et al. Frequency of HER-2 Positivity in Rectal Cancer and Prognosis. The American Journal of Surgical Pathology. 2013;37(4):522. doi: 10.1097/PAS.0b013e318272ff4d.Osako T. et al. Immunohistochemical Study of c-erbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival. OCL. 1998;55(6):548–555. doi: 10.1159/000011911.Osako T. et al. Immunohistochemical Study of c-erbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival. OCL. 1998;55(6):548–555. doi: 10.1159/000011911.Kapitanovic S. et al. The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology. 1997;112(4):1103–1113. Available at: https://www.draganprimorac.com/wp-content/uploads/2012/08/Theexpression-of-HER2-neu-gene-Gastroenterology-1997.pdf.Kapitanovic S. et al. The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology. 1997;112(4):1103–1113. Available at: https://www.draganprimorac.com/wp-content/uploads/2012/08/Theexpression-of-HER2-neu-gene-Gastroenterology-1997.pdf.Sartore-Bianchi A. et al. Dual-targeted therapy with trastuzumab and lapatinib in treatmentrefractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. The Lancet Oncology. 2016;17(6):738–746. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1470204516001509.Sartore-Bianchi A. et al. Dual-targeted therapy with trastuzumab and lapatinib in treatmentrefractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. The Lancet Oncology. 2016;17(6):738–746. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1470204516001509.Hainsworth J.D. et al. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. Journal of Clinical Oncology. 2018;(36):536–544. doi: 10.1200/JCO.2017.75.3780.Hainsworth J.D. et al. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. Journal of Clinical Oncology. 2018;(36):536–544. doi: 10.1200/JCO.2017.75.3780.Ramanathan R.K. et al. Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial. Cancer investigation. 2004;22(6):858–865. Available at: https://www.tandfonline.com/doi/full/10.1081/CNV-200039645.Ramanathan R.K. et al. Low overexpression of HER-2/PPPNeu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin®) and irinotecan as therapy. A phase II trial. Cancer investigation. 2004;22(6):858–865. Available at: https://www.tandfonline.com/doi/full/10.1081/CNV-200039645.Rubinson D.A. et al. Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: Results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients. Invest New Drugs. 2014;32(1):113–122. Available at: https://link.springer.com/article/10.1007%2Fs10637-013-9956-5.Rubinson D.A. et al. Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: Results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients. Invest New Drugs. 2014;32(1):113–122. Available at: https://link.springer.com/article/10.1007%2Fs10637-013-9956-5.Clark J., Niedzwiecki D., Hollis D. Phase-II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. Onkologie. 2003;23:13–46.Clark J., Niedzwiecki D., Hollis D. Phase-II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. Onkologie. 2003;23:13–46.Siena S. et al. HER2 amplification as a ‘molecular bait’ for trastuzumab-emtansine (T-DM1) precision chemotherapy to overcome antiHER2 resistance in HER2 positive metastatic colorectal cancer: The HERACLES-RESCUE trial. JCO. 2016;34(4_suppl.):TPS774–TPS774. doi: 10.1200/jco.2016.34.4_suppl.tps774.Siena S. et al. HER2 amplification as a ‘molecular bait’ for trastuzumab-emtansine (T-DM1) precision chemotherapy to overcome antiHER2 resistance in HER2 positive metastatic colorectal cancer: The HERACLES-RESCUE trial. JCO. 2016;34(4_suppl.):TPS774–TPS774. doi: 10.1200/jco.2016.34.4_suppl.tps774.Strickler J.H. et al. A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER). JCO. 2017;35(15_suppl.):TPS3624–TPS3624. doi: 10.1200/JCO.2017.35.15_suppl.TPS3624.Strickler J.H. et al. A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER). JCO. 2017;35(15_suppl.):TPS3624–TPS3624. doi: 10.1200/JCO.2017.35.15_suppl.TPS3624.Diaz L.A. et al. Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC. JCO. 2017;35(15_suppl.):3071–3071. doi: 10.1200/JCO.2017.35.15_suppl.3071.Diaz L.A. et al. Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC. JCO. 2017;35(15_suppl.):3071–3071. doi: 10.1200/JCO.2017.35.15_suppl.3071.Overman M.J. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. The Lancet Oncology. 2017;18(9):1182–1191. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1470204517304229.Overman M.J. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. The Lancet Oncology. 2017;18(9):1182–1191. Available at: https://linkinghub.elsevier.com/retrieve/pii/S1470204517304229.Corcoran R.B. et al. Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAFV600EMutant Colorectal Cancer. Cancer Discov. 2018;8(4):428–443. doi: 10.1158/2159-8290.CD-17-1226.Corcoran R.B. et al. Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAFV600EMutant Colorectal Cancer. Cancer Discov. 2018;8(4):428–443. doi: 10.1158/2159-8290.CD-17-1226.Kopetz S. et al. Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol. 2015;33(34):4032–4038. doi: 10.1200/JCO.2015.63.2497.Kopetz S. et al. Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol. 2015;33(34):4032–4038. doi: 10.1200/JCO.2015.63.2497.Gelsomino F., Barbolini M., Spallanzani A., Pugliese G., Cascinu S. The evolving role of microsatellite instability in colorectal cancer: A review. Cancer Treat Rev. 2016;(51):19-26. doi: 10.1016/j.ctrv.2016.10.005.Gelsomino F., Barbolini M., Spallanzani A., Pugliese G., Cascinu S. The evolving role of microsatellite instability in colorectal cancer: A review. Cancer Treat Rev. 2016;(51):19-26. doi: 10.1016/j.ctrv.2016.10.005.Brim H., Mokarram P., Naghibalhossaini F., Saberi-Firoozi M., Al-Mandhari M., Al-Mawaly K., et al. Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study. Mol Cancer. 200821;7:68. doi: 10.1186/1476-4598-7-68.Brim H., Mokarram P., Naghibalhossaini F., Saberi-Firoozi M., Al-Mandhari M., Al-Mawaly K., et al. Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study. Mol Cancer. 200821;7:68. doi: 10.1186/1476-4598-7-68.

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