tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2023-13-4-60-68tumors-1157Research ArticleОБЗОРЫ И АНАЛИТИКАREVIEWS AND ANALYSISЛекарственное лечение метастатического рака поджелудочной железыSystemic therapy for metastatic pancreatic cancerЧихареваЯ. Е.ChikharevaY. E.

Яна Е. Чихарева, врач-онколог онкологического отделения лекарственных методов лечения (химиотерапевтического) №2 отдела лекарственного лечения НИИ клинической онкологии им. академика РАН и РАМН Н.Н. Трапезникова

Москва

Yana E. Chikhareva, Сlinical oncologist, Chemotherapy Department No. 2

Moscow

yanachikhareva@outlook.comФедянинМ. Ю.FedyaninM. Yu.

Михаил Ю. Федянин, д. м. н., руководитель химиотерапевтической службы;

старший научный сотрудник отделения лекарственных методов лечения (химиотерапевтическое) №2

Москва

Mikhail Yu. Fedyanin, MD, PhD, DSc, Senior Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2;

Head of Chemotherapy Service

Moscow

fedianinmu@mail.ruБазинИ. С.BazinI. S.

Игорь С. Базин, д. м. н., ведущий научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) №2 отдела лекарственного лечения НИИ клинической онкологии им. академика РАН и РАМН Н.Н. Трапезникова

Москва

Igor S. Bazin, MD, PhD, DSc, Senior Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2

Moscow

bazin_onk@mail.ruПокатаевИ. А.PokataevI. A.

Илья А. Покатаев, д. м. н., руководитель службы химиотерапевтического лечения

Москва

Ilya A. Pokataev, MD, PhD, DSc, Head of the Medical Oncology Department

Moscow

pokia@mail.ruТрякинА. А.TryakinA. A.

Алексей А. Трякин, д. м. н., заместитель директора по научной работе, заведующий онкологическим отделением лекарственных методов лечения (химиотерапевтическое) №2

Москва

Alexey A. Tryakin, MD, PhD, DSc, Deputy Director for Research, Head of Chemotherapy Department No. 2

Moscow

atryakin@gmail.comФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN. N. Blokhin National Medical Research Center of OncologyRussian FederationГБУЗ «ММКЦ «Коммунарка» ДЗМ»; ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN. N. Blokhin National Medical Research Center of Oncology; Kommunarka Moscow Medical and Surgical CenterRussian FederationГБУЗ «Городская клиническая онкологическая больница № 1» ДЗ МосквыРоссияCity Clinical Oncology Hospital No. 1Russian Federation2023091020231346068Copyright © Чихарева Я.Е., Федянин М.Ю., Базин И.С., Покатаев И.А., Трякин А.А., 20242024Чихарева Я.Е., Федянин М.Ю., Базин И.С., Покатаев И.А., Трякин А.А.Chikhareva Y.E., Fedyanin M.Y., Bazin I.S., Pokataev I.A., Tryakin 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.malignanttumors.org/jour/article/view/1157

Рак поджелудочной железы является агрессивным заболеванием с крайне неблагоприятным прогнозом. При метастатическом процессе единственным эффективным методом лечения этой опухоли является химиотерапия. Внедрение комбинированных режимов химиотерапии и развитие молекулярной онкологии в последние годы изменили подходы к лечению этого заболевания. В данном обзоре представлены актуальные литературные данные, а также данные НМИЦ онкологии Н.Н. Блохина, касающиеся современных аспектов лечения метастатического рака поджелудочной железы.

Pancreatic cancer is an aggressive disease with an extremely unfavorable prognosis. The only effective method of treatment for this cancer is chemotherapy. The introduction of combined chemotherapy regimens and the development of molecular oncology in recent years have changed approaches to the treatment of this tumor. This review presents current literature data, as well as the data from the N. N. Blokhin National Medical Research Center of Oncology, concerning modern aspects of the treatment for metastatic pancreatic cancer.

аденокарцинома поджелудочной железылекарственная терапияpancreatic adenocarcinomasystemic therapyReferencesPancreatic Cancer — Cancer Stat Facts [Electronic resource]. URL: https://seer.cancer.gov/statfacts/html/pancreas.html (accessed: 21.01.2023).Pancreatic Cancer — Cancer Stat Facts [Electronic resource]. URL: https://seer.cancer.gov/statfacts/html/pancreas.html (accessed: 21.01.2023).Burris H.A. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. // Journal of Clinical Oncology. 1997. Vol. 15, №6.Burris H.A. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. // Journal of Clinical Oncology. 1997. Vol. 15, №6.Heinemann V. et al. Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer // Journal of Clinical Oncology. 2006. Vol. 24, № 24.Heinemann V. et al. Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer // Journal of Clinical Oncology. 2006. Vol. 24, № 24.Rocha Lima C.M. et al. Irinotecan Plus Gemcitabine Results in No Survival Advantage Compared With Gemcitabine Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer Despite Increased Tumor Response Rate // Journal of Clinical Oncology. 2004. Vol. 22, № 18.Rocha Lima C.M. et al. Irinotecan Plus Gemcitabine Results in No Survival Advantage Compared With Gemcitabine Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer Despite Increased Tumor Response Rate // Journal of Clinical Oncology. 2004. Vol. 22, № 18.Moore M.J. et al. Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group // Journal of Clinical Oncology. 2007. Vol. 25, № 15.Moore M.J. et al. Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group // Journal of Clinical Oncology. 2007. Vol. 25, № 15.Kordes S. et al. Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer // Cancer Chemother Pharmacol. 2015. Vol. 75, №6.Kordes S. et al. Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer // Cancer Chemother Pharmacol. 2015. Vol. 75, №6.Conroy T. et al. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer // New England Journal of Medicine. 2011. Vol. 364, № 19.Conroy T. et al. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer // New England Journal of Medicine. 2011. Vol. 364, № 19.von Hoff D.D. et al. Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine // New England Journal of Medicine. 2013. Vol. 369, № 18.von Hoff D.D. et al. Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine // New England Journal of Medicine. 2013. Vol. 369, № 18.Wang-Gillam A. et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial // The Lancet. 2016. Vol. 387, № 10018.Wang-Gillam A. et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial // The Lancet. 2016. Vol. 387, № 10018.Sohal D.P. S. et al. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial // JAMA Oncol. American Medical Association, 2021. Vol. 7, №3. P. 421–427.Sohal D.P. S. et al. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial // JAMA Oncol. American Medical Association, 2021. Vol. 7, №3. P. 421–427.Servetto A. et al. Use of FOLFIRINOX or Nab-Paclitaxel Plus Gemcitabine for the Treatment of Locally Advanced Pancreatic Adenocarcinoma: A Single Institution Observational Study // Cancers (Basel). 2021. Vol. 13, № 19. P. 4939.Servetto A. et al. Use of FOLFIRINOX or Nab-Paclitaxel Plus Gemcitabine for the Treatment of Locally Advanced Pancreatic Adenocarcinoma: A Single Institution Observational Study // Cancers (Basel). 2021. Vol. 13, № 19. P. 4939.Pusceddu S. et al. Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis // Cancers (Basel). 2019. Vol. 11, №4.Pusceddu S. et al. Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis // Cancers (Basel). 2019. Vol. 11, №4.Chiorean E.G. et al. Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review // Therapeutic Advances in Medical Oncology. SAGE Publications Inc., 2019. Vol. 11.Chiorean E.G. et al. Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review // Therapeutic Advances in Medical Oncology. SAGE Publications Inc., 2019. Vol. 11.Покатаев И.А. Консервативное лечение пациентов с местнораспространенным и метастатическим раком поджелудочной железы: автореф. дис. док. мед. наук 14.01.12 - 2020. – 25-27 с.Покатаев И.А. Консервативное лечение пациентов с местнораспространенным и метастатическим раком поджелудочной железы: автореф. дис. док. мед. наук 14.01.12 - 2020. – 25-27 с.Wainberg Z.A. et al. A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluoro-uracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-nä ıve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). 2023.Wainberg Z.A. et al. A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluoro-uracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-nä ıve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). 2023.Wang Y., Camateros P., Cheung W.Y. A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers // J Gastrointest Cancer. Humana Press Inc., 2019. Vol. 50, №1. P. 62–68.Wang Y., Camateros P., Cheung W.Y. A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers // J Gastrointest Cancer. Humana Press Inc., 2019. Vol. 50, №1. P. 62–68.Papneja N. et al. Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-Paclitaxel: A Population-Based Cohort Study // Pancreas. Lippincott Williams and Wilkins, 2019. Vol. 48, №7. P. 920–926.Papneja N. et al. Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-Paclitaxel: A Population-Based Cohort Study // Pancreas. Lippincott Williams and Wilkins, 2019. Vol. 48, №7. P. 920–926.Kordes M. et al. Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort // Cancers (Basel). 2019. Vol. 11, №9.Kordes M. et al. Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort // Cancers (Basel). 2019. Vol. 11, №9.Cartwright T.H. et al. Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting // Drugs Real World Outcomes. Springer International Publishing, 2018. Vol. 5, №3. P. 149–159.Cartwright T.H. et al. Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting // Drugs Real World Outcomes. Springer International Publishing, 2018. Vol. 5, №3. P. 149–159.de Dosso S. et al. Treatment landscape of metastatic pancreatic cancer // Cancer Treat Rev. 2021. Vol. 96.de Dosso S. et al. Treatment landscape of metastatic pancreatic cancer // Cancer Treat Rev. 2021. Vol. 96.Tsang E.S. et al. Outcomes and Characteristics of Patients Receiving Second-line Therapy for Advanced Pancreatic Cancer // Am J Clin Oncol. 2019. Vol. 42, №2.Tsang E.S. et al. Outcomes and Characteristics of Patients Receiving Second-line Therapy for Advanced Pancreatic Cancer // Am J Clin Oncol. 2019. Vol. 42, №2.Bachet J.-B. et al. Second- and third-line chemotherapy in patients with metastatic pancreatic adenocarcinoma: Feasibility and potential benefits in a retrospective series of 117 patients // Gastroenterol Clin Biol. 2009. Vol. 33, № 10–11.Bachet J.-B. et al. Second- and third-line chemotherapy in patients with metastatic pancreatic adenocarcinoma: Feasibility and potential benefits in a retrospective series of 117 patients // Gastroenterol Clin Biol. 2009. Vol. 33, № 10–11.Oettle H. et al. Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial // Journal of Clinical Oncology. 2014. Vol. 32, № 23.Oettle H. et al. Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial // Journal of Clinical Oncology. 2014. Vol. 32, № 23.Gill S. et al. PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy // Journal of Clinical Oncology. 2016. Vol. 34, № 32.Gill S. et al. PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy // Journal of Clinical Oncology. 2016. Vol. 34, № 32.Portal A. et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort // Br J Cancer. 2015. Vol. 113, №7.Portal A. et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort // Br J Cancer. 2015. Vol. 113, №7.Mita N. et al. Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure // J Clin Med. 2019. Vol. 8, №6.Mita N. et al. Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure // J Clin Med. 2019. Vol. 8, №6.Tsang E.S. et al. Real-world Outcomes Among Patients Treated With Gemcitabine-based Therapy Post-FOLFIRINOX Failure in Advanced Pancreatic Cancer // Am J Clin Oncol. 2019. Vol. 42, № 12.Tsang E.S. et al. Real-world Outcomes Among Patients Treated With Gemcitabine-based Therapy Post-FOLFIRINOX Failure in Advanced Pancreatic Cancer // Am J Clin Oncol. 2019. Vol. 42, № 12.Zhang H. et al. Efficacy and Tolerability of Second-line Nab-paclitaxel and Gemcitabine After Failure of First-line FOLFIRINOX for Advanced Pancreas Cancer: A Single-institution Experience // Clin Colorectal Cancer. 2018. Vol. 17, №3.Zhang H. et al. Efficacy and Tolerability of Second-line Nab-paclitaxel and Gemcitabine After Failure of First-line FOLFIRINOX for Advanced Pancreas Cancer: A Single-institution Experience // Clin Colorectal Cancer. 2018. Vol. 17, №3.Nguyen K.T. et al. Gemcitabine/nab-paclitaxel as second-line therapy following FOLFIRINOX in metastatic/advanced pancreatic cancer—retrospective analysis of response // J Gastrointest Oncol. 2017. Vol. 8, №3.Nguyen K.T. et al. Gemcitabine/nab-paclitaxel as second-line therapy following FOLFIRINOX in metastatic/advanced pancreatic cancer—retrospective analysis of response // J Gastrointest Oncol. 2017. Vol. 8, №3.el Rassy E. et al. Could the combination of Nab-paclitaxel plus gemcitabine salvage metastatic pancreatic adenocarcinoma after folfirinox failure? A single institutional retrospective analysis // Clin Res Hepatol Gastroenterol. 2017. Vol. 41, №2.el Rassy E. et al. Could the combination of Nab-paclitaxel plus gemcitabine salvage metastatic pancreatic adenocarcinoma after folfirinox failure? A single institutional retrospective analysis // Clin Res Hepatol Gastroenterol. 2017. Vol. 41, №2.de Jesus V.H. F. et al. Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer // Ther Adv Med Oncol. 2020. Vol. 12.de Jesus V.H. F. et al. Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer // Ther Adv Med Oncol. 2020. Vol. 12.Assaf E. et al. 5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) as Second-Line Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma // Oncology. 2011. Vol. 80, №5–6.Assaf E. et al. 5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) as Second-Line Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma // Oncology. 2011. Vol. 80, №5–6.Kobayashi N. et al. Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure // Medicine. 2017. Vol. 96, № 19.Kobayashi N. et al. Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure // Medicine. 2017. Vol. 96, № 19.Kim J.H. et al. Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study // Cancer Commun. 2018. Vol. 38, №1.Kim J.H. et al. Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study // Cancer Commun. 2018. Vol. 38, №1.Chung M.J. et al. Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer // World J Gastrointest Oncol. 2018. Vol. 10, № 12.Chung M.J. et al. Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer // World J Gastrointest Oncol. 2018. Vol. 10, № 12.Sawada M. et al. Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer // BMC Cancer. 2020. Vol. 20, №1.Sawada M. et al. Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer // BMC Cancer. 2020. Vol. 20, №1.Matsumoto T. et al. FOLFIRINOX for Advanced Pancreatic Cancer Patients After Nab-Paclitaxel Plus Gemcitabine Failure // Pancreas. 2020. Vol. 49, №4.Matsumoto T. et al. FOLFIRINOX for Advanced Pancreatic Cancer Patients After Nab-Paclitaxel Plus Gemcitabine Failure // Pancreas. 2020. Vol. 49, №4.Bullock A. et al. Capecitabine and oxaliplatin as first and second line treatment for locally advanced and metastatic pancreatic ductal adenocarcinoma // J Gastrointest Oncol. 2017. Vol. 8, №6.Bullock A. et al. Capecitabine and oxaliplatin as first and second line treatment for locally advanced and metastatic pancreatic ductal adenocarcinoma // J Gastrointest Oncol. 2017. Vol. 8, №6.Chung K.H. et al. Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy // Gut Liver. 2017. Vol. 11, №2.Chung K.H. et al. Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy // Gut Liver. 2017. Vol. 11, №2.Bayoglu I.V. et al. Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer // Asian Pacific Journal of Cancer Prevention. 2014. Vol. 15, № 17.Bayoglu I.V. et al. Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer // Asian Pacific Journal of Cancer Prevention. 2014. Vol. 15, № 17.Park S.J. et al. Oral chemotherapy for second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer // World J Gastrointest Oncol. 2019. Vol. 11, № 11.Park S.J. et al. Oral chemotherapy for second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer // World J Gastrointest Oncol. 2019. Vol. 11, № 11.Sonbol M.B. et al. Second-line treatment in patients with pancreatic ductal adenocarcinoma: A meta-analysis // Cancer. 2017. Vol. 123, № 23.Sonbol M.B. et al. Second-line treatment in patients with pancreatic ductal adenocarcinoma: A meta-analysis // Cancer. 2017. Vol. 123, № 23.Abbassi R., Algül H. Palliative chemotherapy in pancreatic cancer—treatment sequences // Transl Gastroenterol Hepatol. 2019. Vol. 4.Abbassi R., Algül H. Palliative chemotherapy in pancreatic cancer—treatment sequences // Transl Gastroenterol Hepatol. 2019. Vol. 4.Dean A.P. et al. Gemcitabine and nab-paclitaxel retreatment as a third-line therapy following second-line FOLFIRINOX for advanced pancreatic adenocarcinoma. // Journal of Clinical Oncology. 2019. Vol. 37, № 15_suppl.Dean A.P. et al. Gemcitabine and nab-paclitaxel retreatment as a third-line therapy following second-line FOLFIRINOX for advanced pancreatic adenocarcinoma. // Journal of Clinical Oncology. 2019. Vol. 37, № 15_suppl.Golan T. et al. Overall survival from the phase 3 POLO trial: Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. // Journal of Clinical Oncology. 2021. Vol. 39, № 3_suppl. P. 378–378.Golan T. et al. Overall survival from the phase 3 POLO trial: Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. // Journal of Clinical Oncology. 2021. Vol. 39, № 3_suppl. P. 378–378.Golan T. et al. Maintenance Olaparib for Germline BRCA -Mutated Metastatic Pancreatic Cancer // New England Journal of Medicine. 2019. Vol. 381, №4.Golan T. et al. Maintenance Olaparib for Germline BRCA -Mutated Metastatic Pancreatic Cancer // New England Journal of Medicine. 2019. Vol. 381, №4.Marabelle A. et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study // Journal of Clinical Oncology. 2020. Vol. 38, №1.Marabelle A. et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study // Journal of Clinical Oncology. 2020. Vol. 38, №1.Waddell N. et al. Whole genomes redefine the mutational landscape of pancreatic cancer // Nature. 2015. Vol. 518, № 7540.Waddell N. et al. Whole genomes redefine the mutational landscape of pancreatic cancer // Nature. 2015. Vol. 518, № 7540.Humphris J.L. et al. Hypermutation In Pancreatic Cancer // Gastroenterology. W.B. Saunders, 2017. Vol. 152, №1. P. 68-74. e2.Humphris J.L. et al. Hypermutation In Pancreatic Cancer // Gastroenterology. W.B. Saunders, 2017. Vol. 152, №1. P. 68-74. e2.Allen M.J. et al. Molecular characterisation of pancreatic ductal adenocarcinoma with NTRK fusions and review of the literature // J Clin Pathol. 2021. P. jclinpath-2021-207781.Allen M.J. et al. Molecular characterisation of pancreatic ductal adenocarcinoma with NTRK fusions and review of the literature // J Clin Pathol. 2021. P. jclinpath-2021-207781.Drilon A. et al. Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children // New England Journal of Medicine. Massachusetts Medical Society, 2018. Vol. 378, №8. P. 731–739.Drilon A. et al. Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children // New England Journal of Medicine. Massachusetts Medical Society, 2018. Vol. 378, №8. P. 731–739.Doebele R.C. et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials // Lancet Oncol. Lancet Publishing Group, 2020. Vol. 21, №2. P. 271–282.Doebele R.C. et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials // Lancet Oncol. Lancet Publishing Group, 2020. Vol. 21, №2. P. 271–282.Strickler J.H. et al. Sotorasib in KRAS p. G12C–Mutated Advanced Pancreatic Cancer // New England Journal of Medicine. 2023. Vol. 388, №1. P. 33–43.Strickler J.H. et al. Sotorasib in KRAS p. G12C–Mutated Advanced Pancreatic Cancer // New England Journal of Medicine. 2023. Vol. 388, №1. P. 33–43.Philip P.A. et al. Molecular Characterization of KRAS Wild-type Tumors in Patients with Pancreatic Adenocarcinoma // Clinical Cancer Research. 2022. Vol. 28, № 12. P. 2704–2714.Philip P.A. et al. Molecular Characterization of KRAS Wild-type Tumors in Patients with Pancreatic Adenocarcinoma // Clinical Cancer Research. 2022. Vol. 28, № 12. P. 2704–2714.Schultheis B. et al. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen inKRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study // Annals of Oncology. 2017. Vol. 28, № 10. P. 2429–2435.Schultheis B. et al. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen inKRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study // Annals of Oncology. 2017. Vol. 28, № 10. P. 2429–2435.Qin S. et al. Nimotuzumab combined with gemcitabine versus gemcitabine in K-RAS wild-type locally advanced or metastatic pancreatic cancer: A prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial. // Journal of Clinical Oncology. 2022. Vol. 40, № 17_suppl. P. LBA4011–LBA4011.Qin S. et al. Nimotuzumab combined with gemcitabine versus gemcitabine in K-RAS wild-type locally advanced or metastatic pancreatic cancer: A prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial. // Journal of Clinical Oncology. 2022. Vol. 40, № 17_suppl. P. LBA4011–LBA4011.da Cunha Santos G, Dhani N, Tu D, et al. Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Canada Clinical Trials Group Study PA. 3. Cancer 2010; 116: 5599–5607.da Cunha Santos G, Dhani N, Tu D, et al. Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Canada Clinical Trials Group Study PA. 3. Cancer 2010; 116: 5599–5607.Wang JP, Wu C-Y, Yeh Y-C, et al. Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial. Oncotarget 2015; 6: 18162–18173.Wang JP, Wu C-Y, Yeh Y-C, et al. Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial. Oncotarget 2015; 6: 18162–18173.Chikhareva, Y., et al. P-333 Retrospective analysis of second-line chemotherapy after Folfirinox failure in advanced pancreatic cancer. Annals of Oncology, 34, S131.Chikhareva, Y., et al. P-333 Retrospective analysis of second-line chemotherapy after Folfirinox failure in advanced pancreatic cancer. Annals of Oncology, 34, S131.

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