medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2024-32-14-18medalphabet-4104Research ArticleСтатьиСобственный опыт применения двойной анти-HER2 терапии при раке внутрипеченочных желчных протоковOwn experience of using anti-HER2 therapy for cancer of the intrahepatic cholangiocarcinomahttps://orcid.org/0000-0003-3532-6476ГолубевП. В.GolubevP. V.

Голубев Павел Вячеславович, к.м.н., врач-онколог химиотерапевтического отделения № 2 Онкологического центра № 1

Москва 

Golubev Pavel V., PhD Med, oncologist at Chemotherapy Dept No 2, Oncology Center No 1

Moscow 

golubev194@gmail.comhttps://orcid.org/0009-0007-2856-5176КузьминаЕ. С.KuzminaE. S.

Кузьмина Евгения Сергеевна, заведующая химиотерапевтическим отделением № 2 Онкологического центра № 1

Москва 

Kuzmina Evgeniya S., head of Chemotherapy Dept No 2, Oncology Center No 1 

Moscow 

https://orcid.org/0000-0001-9864-3837ПокатаевИ. А.PokataevI. A.

Покатаев Илья Анатольевич, д.м.н., руководитель службы химиотерапевтического лечения Онкологического центра № 1

Москва 

Pokataev Ilya A., DM Sci (habil.), head of Chemotherapy Treatment Service, Oncology Center No 1

Moscow 

https://orcid.org/0000-0002-0633-1738ГолубеваС. А.GolubevaS. A.

Голубева Софья Артемовна, врач-онколог отделения комбинированных методов лечения № 1

Москва 

Golubeva Sofia A., oncologist at Combined Treatment Dept No 1 

Moscow 

https://orcid.org/0000-0002-9189-1835КонторовичД. С.KontorovichD. S.

Конторович Дарья Сергеевна, врач-рентгенолог отделения лучевой диагностики Онкологического центра № 1

Москва 

Kontorovich Daria S., radiologist at Dept of Radiation Diagnostics, Oncology Center No 1

Moscow 

https://orcid.org/0000-0002-5569-3655СыдыковаР. С.SydykovaR. S.

Сыдыкова Розана Саматовна, врач-онколог химиотерапевтического отделения № 2 Онкологического центра № 1

Москва 

Sydykova Rozana S., oncologist at Chemotherapy Dept No 2, Oncology Center No 1 

Moscow 

https://orcid.org/0009-0003-9954-4584ПартсС. А.PartsS. A.

Партс Сергей Адольфович, к.м.н., заместитель главного врача по онкологии 

Москва 

Parts Sergey A., PhD Med, deputy chief physician for Oncology 

Moscow 

https://orcid.org/0000-0002-6619-6179ГалкинВ. Н.GalkinV. N.

Галкин Всеволод Николаевич, д.м.н., профессор, главный врач 

Москва 

Galkin Vsevolod N., DM Sci (habil.), professor, chief physician 

Moscow 

ГБУЗ города Москвы «Городская клиническая больница имени С.С. Юдина Департамента здравоохранения города Москвы»РоссияMoscow City Hospital named after S.S. YudinRussian FederationМосковский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияP.A. Herzen Moscow Oncology Research Institute – Branch of National Medical Radiology Research CenterRussian Federation202421012025032Диагностика и онкотерапия (4)1418Copyright © Голубев П.В., Кузьмина Е.С., Покатаев И.А., Голубева С.А., Конторович Д.С., Сыдыкова Р.С., Партс С.А., Галкин В.Н., 20252025Голубев П.В., Кузьмина Е.С., Покатаев И.А., Голубева С.А., Конторович Д.С., Сыдыкова Р.С., Партс С.А., Галкин В.Н.Golubev P.V., Kuzmina E.S., Pokataev I.A., Golubeva S.A., Kontorovich D.S., Sydykova R.S., Parts S.A., Galkin V.N.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-alphabet.com/jour/article/view/4104

Рак билиарного тракта является редким и одним из наиболее агрессивных злокачественных новообразований. Основным методом радикального лечения является хирургический. Однако, только у 1/3 больных возможно применение данного подхода, остальные же пациенты имеют нерезектабельный, местно-распространенный или уже метастатический процесс. Лечебной тактикой данной группы больных является системная лекарственная противоопухолевая терапия. В данной статье мы представляем описание клинического случая эффективного лечения пациента с распространенной внутрипеченочной холангиокарциномой с использованием не только стандартных цитостатиков, но и современных таргетных препаратов.

Cancer of the biliary tract is rare and one of the most aggressive malignancies. The main method of radical treatment is surgical. However, only 1/3 of patients can use this approach, while the rest of the patients have an unresectable, locally widespread or already metastatic process. The therapeutic tactic of this group of patients is systemic drug antitumor therapy. In this article, we present a description of a clinical case of effective treatment of a patient with advanced intrahepatic cholangiocarcinoma using not only standard cytostatics, but also modern targeted drugs.

холангиокарциномарак желчного протокарак внутрипеченочного желчного протокаанти-HER2-терапиятрастузумабпертузумабcholangiocarcinomaintrahepatic cholangiocarcinomaanti-HER2-therapytrastuzumabpertuzumabReferencesBuettner S., van Vugt J.L., Ijzermans J.N., Groot Koerkamp B. Intrahepatic cholangiocarcinoma: currentperspectives. OncoTargetsTher. 2017; 10: 1131–1142. DOI: 10.2147/OTT.S93629.Buettner S., van Vugt J.L., Ijzermans J.N., Groot Koerkamp B. Intrahepatic cholangiocarcinoma: currentperspectives. OncoTargetsTher. 2017; 10: 1131–1142. DOI: 10.2147/OTT.S93629.Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol. 2004;40(3):472–477.https://doi.org/10.1016/j.jhep.2003.11.030Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol. 2004;40(3):472–477.https://doi.org/10.1016/j.jhep.2003.11.030Khan SA, Emadossadaty S, Ladep NG, Thomas HC, Elliott P, Taylor-Robinson SD et al. Rising trends in cholangiocarcinoma: is the ICD classifi cation system misleading us? J Hepatol. 2012;56(4):848–854.https://doi.org/10.1016/j.jhep.2011.11.015Khan SA, Emadossadaty S, Ladep NG, Thomas HC, Elliott P, Taylor-Robinson SD et al. Rising trends in cholangiocarcinoma: is the ICD classifi cation system misleading us? J Hepatol. 2012;56(4):848–854.https://doi.org/10.1016/j.jhep.2011.11.015Shin HR, Oh JK, Lim MK, Shin A, Kong HJ, Jung KW et al. Descriptive epidemiology of cholangiocarcinoma and clonorchiasis in Korea. J Korean Med Sci. 2010;25(7):1011–1016. https://doi.org/10.3346/jkms.2010.25.7.1011Shin HR, Oh JK, Lim MK, Shin A, Kong HJ, Jung KW et al. Descriptive epidemiology of cholangiocarcinoma and clonorchiasis in Korea. J Korean Med Sci. 2010;25(7):1011–1016. https://doi.org/10.3346/jkms.2010.25.7.1011Bertuccio P, Bosetti C, Levi F, Decarli A, Negri E, Vecchia CL. A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol. 2013;24(6):1667–1674. https://doi.org/10.1093/annonc/mds652Bertuccio P, Bosetti C, Levi F, Decarli A, Negri E, Vecchia CL. A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol. 2013;24(6):1667–1674. https://doi.org/10.1093/annonc/mds652Tyson GL, El-Serag HB. Risk factors for cholangiocarcinoma. Hepatology. 2011;54(1):173–184. https://doi.org/10.1002/hep.24351Tyson GL, El-Serag HB. Risk factors for cholangiocarcinoma. Hepatology. 2011;54(1):173–184. https://doi.org/10.1002/hep.24351Buettner S., van Vugt J.L., Ijzermans J.N., Groot Koerkamp B. Intrahepatic cholangiocarcinoma: current perspectives. OncoTargetsTher. 2017; 10: 1131–1142. DOI: 10.2147/OTT.S93629.Buettner S., van Vugt J.L., Ijzermans J.N., Groot Koerkamp B. Intrahepatic cholangiocarcinoma: current perspectives. OncoTargetsTher. 2017; 10: 1131–1142. DOI: 10.2147/OTT.S93629.Гурмиков Б. Н., Коваленко Ю. А., Пайчадзе А. А., Маринова Л. А., Грицкевич А. А., Чжао А.В. Отдаленные результаты хирургического лечения внутрипеченочного холангиоцеллюлярного рака взависимости от мутационного статуса опухоли. Онкология. Журналим. П.А. Герцена. 2021;10(6):6–13. https://doi.org/10.17116/onkolog2021100616Gurmikov BN, Kovalenko IA, Paichadze AA, Marinova LA, Gritskevich AA, Zhao AV. Long-term results of surgical treatment for intrahepatic cholangiocarcinoma according to the tumor mutation status. P.A. Herzen Journal of Oncology. 2021;10(6):6–13. (In Russ.) https://doi.org/10.17116/onkolog2021100616Valle J., Wasan H., Palmer D. H., Cunningham D., Anthoney A., Maraveyas A. et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–1281. https://doi.org/10.1056/NEJMoa0908721Valle J., Wasan H., Palmer D. H., Cunningham D., Anthoney A., Maraveyas A. et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–1281. https://doi.org/10.1056/NEJMoa0908721Oh D.Y., He A.R., Qin S., Chen L., Okusaka T., Vogel A. et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol. 2022;40(Suppl. 4):378. https://doi.org/10.1200/JCO.2022.40.4_suppl.378.Oh D.Y., He A.R., Qin S., Chen L., Okusaka T., Vogel A. et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol. 2022;40(Suppl. 4):378. https://doi.org/10.1200/JCO.2022.40.4_suppl.378.Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853–1865. doi: 10.1016/S0140–6736(23)00727-4.Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853–1865. doi: 10.1016/S0140–6736(23)00727-4.Савченко ИВ, Бредер ВВ, Стилиди ИС, Лактионов КК, Кудашкин НЕ, Егорова АВ, Чулкова СВ. Вторая линия лекарственной терапии билиарного рака. Медицинский Совет. 2022;(22):136–147. https://doi.org/10.21518/2079–701X-2022-16-22-136-147Savchenko IV, Breder VV, Stilidi IS, Laktionov KK, Kudashkin NE, Egorova AV, Chulkova SV. Second line drug therapy for biliary cancer. Meditsinskiysovet = Medical Council. 2022;(22):136–147. (In Russ.) https://doi.org/10.21518/2079–701X-2022-16-22-136-147Weinberg BA, Xiu J, Lindberg MR, Shields AF, Hwang JJ, Poorman K, Salem ME, Pishvaian MJ, Holcombe RF, Marshall JL, Morse MA. Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets. J Gastrointest Oncology. 2019;10(4):652–662.https://doi.org/10.21037/jgo.2018.08.18Weinberg BA, Xiu J, Lindberg MR, Shields AF, Hwang JJ, Poorman K, Salem ME, Pishvaian MJ, Holcombe RF, Marshall JL, Morse MA. Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets. J Gastrointest Oncology. 2019;10(4):652–662.https://doi.org/10.21037/jgo.2018.08.18Ma B, Meng H, Tian Y, Wang Y, Song T, Zhang T, Wu Q, Cui Y, Li H, Zhang W, Li Q. Distinct clinical and prognostic implication of IDH1/2 mutation and other most frequent mutations in large duct and small duct subtypes of intrahepatic cholangiocarcinoma. BMC cancer. 2020;20(1):318.Ma B, Meng H, Tian Y, Wang Y, Song T, Zhang T, Wu Q, Cui Y, Li H, Zhang W, Li Q. Distinct clinical and prognostic implication of IDH1/2 mutation and other most frequent mutations in large duct and small duct subtypes of intrahepatic cholangiocarcinoma. BMC cancer. 2020;20(1):318.Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, et al. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. CancerDiscov. 2017;7(10):1116–1135. https://doi.org/10.1158/2159–8290.CD-17–0368Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, et al. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. CancerDiscov. 2017;7(10):1116–1135. https://doi.org/10.1158/2159–8290.CD-17–0368Walter D, Hartmann S, Waidmann O. Update on cholangiocarcinoma: Potential impact of genomic studies on clinical management. Z Gastroenterol. 2017;55(6):575–581. https://doi.org/10.1055/s-0043–102581Walter D, Hartmann S, Waidmann O. Update on cholangiocarcinoma: Potential impact of genomic studies on clinical management. Z Gastroenterol. 2017;55(6):575–581. https://doi.org/10.1055/s-0043–102581Goeppert B, Frauenschuh L, Renner M, et al. BRAF V600E-specifi c immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. ModPathol. 2014;27(7):1028–1034. https://doi.org/10.1038/modpathol.2013.206Goeppert B, Frauenschuh L, Renner M, et al. BRAF V600E-specifi c immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. ModPathol. 2014;27(7):1028–1034. https://doi.org/10.1038/modpathol.2013.206Chen MH, Chiang KC, Cheng CT, Huang SC, Chen YY, Chen TW, Yeh TS, Jan YY, Wang HM, Weng JJ, Chang PM, Liu CY, Li CP, Chao Y, Chen MH, Huang CY, Yeh CN. Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma. Oncotarget. 2014;5(9):2372–2389.https://doi.org/10.18632/oncotarget.1706Chen MH, Chiang KC, Cheng CT, Huang SC, Chen YY, Chen TW, Yeh TS, Jan YY, Wang HM, Weng JJ, Chang PM, Liu CY, Li CP, Chao Y, Chen MH, Huang CY, Yeh CN. Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma. Oncotarget. 2014;5(9):2372–2389.https://doi.org/10.18632/oncotarget.1706Javle M, Churi C, Kang HC, Shroff R, Janku F, Surapaneni R, Zuo M, Barrera C, Alshamsi H, Krishnan S, Mishra L, Wolff RA, Kaseb AO, Thomas MB, Siegel AB. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol. 2015;8:58.https://doi.org/10.1186/s13045–015–0155-zJavle M, Churi C, Kang HC, Shroff R, Janku F, Surapaneni R, Zuo M, Barrera C, Alshamsi H, Krishnan S, Mishra L, Wolff RA, Kaseb AO, Thomas MB, Siegel AB. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol. 2015;8:58.https://doi.org/10.1186/s13045–015–0155-zLaw LY. Dramatic response to trastuzumab and paclitaxel in a patient with human epidermal growth factor receptor 2-positive metastatic cholangiocarcinoma. J ClinOncol. 2012;30(27): e271–273. https://doi.org/10.1200/JCO.2012.42.3061Law LY. Dramatic response to trastuzumab and paclitaxel in a patient with human epidermal growth factor receptor 2-positive metastatic cholangiocarcinoma. J ClinOncol. 2012;30(27): e271–273. https://doi.org/10.1200/JCO.2012.42.3061Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–1672. https://doi.org/10.1056/NEJMoa052306Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–1672. https://doi.org/10.1056/NEJMoa052306Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al.; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–697. https://doi.org/10.1016/s0140–6736(10)61121-xBang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al.; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–697. https://doi.org/10.1016/s0140–6736(10)61121-xВторушин С. В., Крахмаль Н. В., Завалишина Л. Э., Кузнецова О.А., Москвина Л. В., Франк Г.А. Определение HER2-статуса карцином различных локализаций. Архив патологии. 2023;85(6):31–46.https://doi.org/10.17116/patol20238506131Vtorushin SV, Krakhmal NV, Zavalishina LE, Kuznetsova OA, Moskvina LV, Frank GA. Assessment of HER2 status of carcinomas of various localizations. Russian Journal of Archive of Pathology. 2023;85(6):31–46. (In Russ.) https://doi.org/10.17116/patol20238506131Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profi les: Results From MyPathway, an Open-Label, Phase IIaMultiple Basket Study. J Clin Oncol. 2018;36(6):536–542. https://doi.org/10.1200/JCO.2017.75.3780Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profi les: Results From MyPathway, an Open-Label, Phase IIaMultiple Basket Study. J Clin Oncol. 2018;36(6):536–542. https://doi.org/10.1200/JCO.2017.75.3780Javle, M., Borad, M. J., Azad, N. S., Kurzrock, R., Abou-Alfa, G. K., George, B., Hainsworth, J., Meric-Bernstam, F., Swanton, C., Sweeney, C. J., Friedman, C. F., Bose, R., Spigel, D. R., Wang, Y., Levy, J., Schulze, K., Cuchelkar, V., Patel, A., & Burris, H. (2021). Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (My Pathway): a multicentre, open-label, phase 2a, multiple basket study. The Lancet Oncology, 22(9), 1290–1300. https://doi.org/10.1016/S1470–2045(21)00336-3Javle, M., Borad, M. J., Azad, N. S., Kurzrock, R., Abou-Alfa, G. K., George, B., Hainsworth, J., Meric-Bernstam, F., Swanton, C., Sweeney, C. J., Friedman, C. F., Bose, R., Spigel, D. R., Wang, Y., Levy, J., Schulze, K., Cuchelkar, V., Patel, A., & Burris, H. (2021). Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (My Pathway): a multicentre, open-label, phase 2a, multiple basket study. The Lancet Oncology, 22(9), 1290–1300. https://doi.org/10.1016/S1470–2045(21)00336-3Lee CK, Chon HJ, Cheon J, Lee MA, Im HS, Jang JS, Kim MH, Park S, Kang B, Hong M, Kim JW, Park HS, Kang MJ, Park YN, Choi HJ. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19–14). Lancet GastroenterolHepatol. 2023 Jan;8(1):56–65. doi: 10.1016/S2468–1253(22)00335-1. Epub 2022 Oct 31.Lee CK, Chon HJ, Cheon J, Lee MA, Im HS, Jang JS, Kim MH, Park S, Kang B, Hong M, Kim JW, Park HS, Kang MJ, Park YN, Choi HJ. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19–14). Lancet GastroenterolHepatol. 2023 Jan;8(1):56–65. doi: 10.1016/S2468–1253(22)00335-1. Epub 2022 Oct 31.Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9–20. doi: 10.1056/NEJMoa2203690.Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9–20. doi: 10.1056/NEJMoa2203690.Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419–2430. doi: 10.1056/NEJMoa2004413.Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419–2430. doi: 10.1056/NEJMoa2004413.Bob T Li et al. Trastuzumab deruxtecan in patients with solid tumoursharbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study. Lancet Oncol. 2024 Jun;25(6):707–719. doi: 10.1016/S1470–2045(24)00140-2.Bob T Li et al. Trastuzumab deruxtecan in patients with solid tumoursharbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study. Lancet Oncol. 2024 Jun;25(6):707–719. doi: 10.1016/S1470–2045(24)00140-2.

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