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Сравнение эффективности терапии регорафенибом и реинтродукции комбинации химиотерапии с анти-EGFR-препаратами в 3-й линии лечения метастатического колоректального рака с диким типом генов RAS и BRAF левосторонней локализации
Сравнение эффективности терапии регорафенибом и реинтродукции комбинации химиотерапии с анти-EGFR-препаратами в 3-й линии лечения метастатического колоректального рака с диким типом генов RAS и BRAF левосторонней локализации
Кузьмина Е.С., Федянин М.Ю., Феоктистова П.С., Лядова М.А., Федоринов Д.С., Магамедова О.Р., Партс С.А., Полянский М.А., Фехтел Е.П., Покатаев И.А., Осипов М.А., Дацюк А.А., Беляк Н.П., Орлова Р.В., Мгарь Е.А., Кузьмин В.М., Глазкова Е.В., Антонова Т.Г., Галкин В.Н. Сравнение эффективности терапии регорафенибом и реинтродукции комбинации химиотерапии с анти-EGFR-препаратами в 3-й линии лечения метастатического колоректального рака с диким типом генов RAS и BRAF левосторонней локализации. Результаты многоцентрового исследования реальной клинической практики. Современная Онкология. 2026;28(1):37–45. DOI: 10.26442/18151434.2026.1.203557
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Аннотация
Цель. Сравнить эффективность и токсичность терапии регорафенибом и повторного применения анти-EGFR моноклональных антител (МАТ) в комбинации с химиотерапией (ХТ) в 3-й линии лечения пациентов с метастатическим колоректальным раком (мКРР) левосторонней локализации с диким типом генов RAS и BRAF, получивших в 1-й линии анти-EGFR таргетную терапию.
Материалы и методы. Проведен ретроспективный анализ базы пациентов с мКРР 5 клиник Российской Федерации. В исследовании было 3 рукава в зависимости от терапии 3-й линии: регорафениб, реинтродукция и речеллендж комбинации ХТ и анти-EGFR МАТ. В настоящей статье мы представляем данные по сравнению реинтродукции и терапии регорафенибом.
Результаты. Идентифицированы 132 пациента с морфологически подтвержденным мКРР левосторонней локализации с диким типом генов RAS и BRAF, получившие 3 линии лекарственной терапии или более с 2014 по 2023 г.: 1-я линия лечения включала анти-EGFR МАТ, в 3-й линии 61 пациенту проводили реинтродукцию комбинации ХТ с анти-EGFR МАТ, 71 пациент получал регорафениб. Контроль над заболеванием в группе реинтродукции описан у 43 (70,5%) пациентов против 18 (25,5%) в группе регорафениба (p=0,0001). Шестимесячная общая выживаемость (ОВ) составила 76% в группе реинтродукции и 55% – в группе регорафениба. Медиана ОВ группе реинтродукции была 18 мес (95% доверительный интервал – ДИ 11,9–24,0 мес), в группе регорафениба – 10 мес (95% ДИ 5,3–14,6 мес; p=0,05 – по log-rank-тесту; p=0,013 – по критерию Бреслоу–Уилкоксона; p=0,024 – по критерию Тарона–Вэра, отношение рисков 1,1, 95% ДИ 0,886–1,408; p=0,349). Выживаемость без прогрессирования (ВБП) была выше в группе реинтродукции ХТ с анти-EGFR МАТ – 6 мес (95% ДИ 5,3–6,6 мес), чем в группе регорафениба – 3 мес (95% ДИ 2,2–3,7 мес; p=0,0001 по log-rank-тесту, отношение рисков 1,23, 95% ДИ 0,997–1,529; p=0,053). Мы не выявили различий в частоте нежелательных явлений всех степеней между исследуемыми группами (p=0,19), а также в частоте развития нежелательных явлений 3–4-й степени (p=0,781).
Заключение. В сравнении с терапией регорафенибом повторное назначение комбинации ХТ с анти-EGFR таргетной терапией в 3-й линии лечения пациентов с левосторонним мКРР с диким типом генов RAS и BRAF ассоциировано с большей частотой контроля болезни и лучшей ВБП и 6-месячной ОВ.
Ключевые слова: колоректальный рак, регорафениб, химиотерапия, анти-EGFR-терапия, анти-EGFR моноклональное антитело, колоректальный рак с диким типом генов RAS и BRAF, ретроспективное исследование, исследования реальной клинической практики
Materials and methods. The database of patients with mCRC from 5 clinics in the Russian Federation was retrospectively analyzed. The study had 3 arms depending on the third-line therapy: regorafenib, reintroduction and rechallenge with the combination of CT and anti-EGFR mAb. In this paper, we present data comparing reintroduction and regorafenib therapy.
Results. 132 patients with morphologically confirmed left-sided mCRC with wild-type RAS and BRAF genes who received at least 3 lines of drug therapy from 2014 to 2023 were identified: the first-line therapy included anti-EGFR mAb; 61 patients were reintroduced with a combination of CT with anti-EGFR mAb, and 71 patients received regorafenib in the third-line therapy. Disease control in the reintroduction group was achieved in 43 (70.5%) patients, compared with 18 (25.5%) in the regorafenib group (p=0.0001). The six-month overall survival (OS) was 76% in the reintroduction group and 55% in the regorafenib group. The median OS in the reintroduction group was 18 months (95% confidence interval [CI] 11.9-24.0 months) and 10 months in the regorafenib group (95% CI 5.3-14.6 months; p=0.05 according to the log-rank test; p=0.013 according to the Breslow-Wilcoxon test; p=0.024 according to the Tarone-Ware test; risk ratio 1.1, 95% CI 0.886-1.408; p=0.349). Progression-free survival (PFS) was higher in the CT reintroduction group with anti-EGFR mAb (6 months [95% CI 5.3-6.6 months] than in the regorafenib group (3 months [95% CI 2.2-3.7 months]; p=0.0001 according to the log-rank test, risk ratio 1.23, 95% CI 0.997-1.529; p=0.053). We found no difference in the incidence of all-grade adverse events between the study groups (p=0.19), nor in the incidence of grade 3-4 adverse events (p=0.781).
Conclusion. Compared with regorafenib therapy, re-administration of a combination of CT with anti-EGFR targeted therapy in the third-line treatment of patients with left-sided mCRC with wild-type RAS and BRAF genes was associated with a higher rate of disease control and better PFS and 6-month OS.
Keywords: colorectal neoplasms, regorafenib, chemotherapy, anti-EGFR therapies, anti-EGFR monoclonal antibody, RAS/BRAF wild-type colorectal cancer, retrospective studies, real-world clinical practice study
Материалы и методы. Проведен ретроспективный анализ базы пациентов с мКРР 5 клиник Российской Федерации. В исследовании было 3 рукава в зависимости от терапии 3-й линии: регорафениб, реинтродукция и речеллендж комбинации ХТ и анти-EGFR МАТ. В настоящей статье мы представляем данные по сравнению реинтродукции и терапии регорафенибом.
Результаты. Идентифицированы 132 пациента с морфологически подтвержденным мКРР левосторонней локализации с диким типом генов RAS и BRAF, получившие 3 линии лекарственной терапии или более с 2014 по 2023 г.: 1-я линия лечения включала анти-EGFR МАТ, в 3-й линии 61 пациенту проводили реинтродукцию комбинации ХТ с анти-EGFR МАТ, 71 пациент получал регорафениб. Контроль над заболеванием в группе реинтродукции описан у 43 (70,5%) пациентов против 18 (25,5%) в группе регорафениба (p=0,0001). Шестимесячная общая выживаемость (ОВ) составила 76% в группе реинтродукции и 55% – в группе регорафениба. Медиана ОВ группе реинтродукции была 18 мес (95% доверительный интервал – ДИ 11,9–24,0 мес), в группе регорафениба – 10 мес (95% ДИ 5,3–14,6 мес; p=0,05 – по log-rank-тесту; p=0,013 – по критерию Бреслоу–Уилкоксона; p=0,024 – по критерию Тарона–Вэра, отношение рисков 1,1, 95% ДИ 0,886–1,408; p=0,349). Выживаемость без прогрессирования (ВБП) была выше в группе реинтродукции ХТ с анти-EGFR МАТ – 6 мес (95% ДИ 5,3–6,6 мес), чем в группе регорафениба – 3 мес (95% ДИ 2,2–3,7 мес; p=0,0001 по log-rank-тесту, отношение рисков 1,23, 95% ДИ 0,997–1,529; p=0,053). Мы не выявили различий в частоте нежелательных явлений всех степеней между исследуемыми группами (p=0,19), а также в частоте развития нежелательных явлений 3–4-й степени (p=0,781).
Заключение. В сравнении с терапией регорафенибом повторное назначение комбинации ХТ с анти-EGFR таргетной терапией в 3-й линии лечения пациентов с левосторонним мКРР с диким типом генов RAS и BRAF ассоциировано с большей частотой контроля болезни и лучшей ВБП и 6-месячной ОВ.
Ключевые слова: колоректальный рак, регорафениб, химиотерапия, анти-EGFR-терапия, анти-EGFR моноклональное антитело, колоректальный рак с диким типом генов RAS и BRAF, ретроспективное исследование, исследования реальной клинической практики
________________________________________________
Materials and methods. The database of patients with mCRC from 5 clinics in the Russian Federation was retrospectively analyzed. The study had 3 arms depending on the third-line therapy: regorafenib, reintroduction and rechallenge with the combination of CT and anti-EGFR mAb. In this paper, we present data comparing reintroduction and regorafenib therapy.
Results. 132 patients with morphologically confirmed left-sided mCRC with wild-type RAS and BRAF genes who received at least 3 lines of drug therapy from 2014 to 2023 were identified: the first-line therapy included anti-EGFR mAb; 61 patients were reintroduced with a combination of CT with anti-EGFR mAb, and 71 patients received regorafenib in the third-line therapy. Disease control in the reintroduction group was achieved in 43 (70.5%) patients, compared with 18 (25.5%) in the regorafenib group (p=0.0001). The six-month overall survival (OS) was 76% in the reintroduction group and 55% in the regorafenib group. The median OS in the reintroduction group was 18 months (95% confidence interval [CI] 11.9-24.0 months) and 10 months in the regorafenib group (95% CI 5.3-14.6 months; p=0.05 according to the log-rank test; p=0.013 according to the Breslow-Wilcoxon test; p=0.024 according to the Tarone-Ware test; risk ratio 1.1, 95% CI 0.886-1.408; p=0.349). Progression-free survival (PFS) was higher in the CT reintroduction group with anti-EGFR mAb (6 months [95% CI 5.3-6.6 months] than in the regorafenib group (3 months [95% CI 2.2-3.7 months]; p=0.0001 according to the log-rank test, risk ratio 1.23, 95% CI 0.997-1.529; p=0.053). We found no difference in the incidence of all-grade adverse events between the study groups (p=0.19), nor in the incidence of grade 3-4 adverse events (p=0.781).
Conclusion. Compared with regorafenib therapy, re-administration of a combination of CT with anti-EGFR targeted therapy in the third-line treatment of patients with left-sided mCRC with wild-type RAS and BRAF genes was associated with a higher rate of disease control and better PFS and 6-month OS.
Keywords: colorectal neoplasms, regorafenib, chemotherapy, anti-EGFR therapies, anti-EGFR monoclonal antibody, RAS/BRAF wild-type colorectal cancer, retrospective studies, real-world clinical practice study
Полный текст
Список литературы
1. Grothey A, Van Cutsem E, Sobrero A, et al.; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-12. DOI:10.1016/S0140-6736(12)61900-X
2. Van Cutsem E, Martinelli E, Cascinu S, et al. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: Results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist. 2019;24(2):185-92. DOI:10.1634/theoncologist.2018-0072
3. Bekaii-Saab TS, Ou FS, Ahn DH. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): A randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070-82. DOI:10.1016/S1470-2045(19)30272-4
4. Lai E, Puzzoni M, Ziranu P, et al.; GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente, Italian Group for the Study of Gastrointestinal Tumors). Long term survival with regorafenib: REALITY (Real Life in Italy) Trial – A GISCAD study. Clin Colorectal Cancer. 2021;20(4):e253-62. DOI:10.1016/j.clcc.2021.07.008
5. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet. 2019;394(10207):1467-80. DOI:10.1016/S0140-6736(19)32319-0
6. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol. 2010;28(31):4697-705. DOI:10.1200/JCO.2009.27.4860
7. Rivera F, Karthaus M, Hecht JR, et al. Final analysis of the randomised PEAK trial: Overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017;32(8):1179-90. DOI:10.1007/s00384-017-2800-1
8. Watanabe J, Muro K, Shitara K, et al. Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial. JAMA. 2023;329(15):1271-82. DOI:10.1001/jama.2023.4428. Erratum in: JAMA. 2023;329(24):2196. DOI:10.1001/jama.2023.10533
9. Van Cutsem E, Lenz HJ, Köhne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33(7):692-700. DOI:10.1200/JCO.2014.59.4812
10. Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408-17. DOI:10.1056/NEJMoa0805019
11. Кузьмина Е.С., Федянин М.Ю., Лядова М.А., и др. Сравнение эффективности и безопасности терапии регорафенибом и анти-EGFR таргетной терапии при метастатическом колоректальном раке. Современная Онкология. 2024;26(3):341-7 [Kuzmina ES, Fedyanin M, Lyadova MA, et al. Comparison of efficacy and safety of regorafenib and anti-EGFR targeted therapy in metastatic colorectal cancer: A retrospective study. Journal of Modern Oncology. 2024;26(3):341-7 (in Russian)]. DOI:10.26442/18151434.2024.3.202889
12. Salvatore L, Bensi M, Vivolo R, et al. Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients. Front Oncol. 2023;13:1125013. DOI:10.3389/fonc.2023.1125013
13. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-75. DOI:10.1016/S1470-2045(14)70330-4
14. Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240-7. DOI:10.1200/JCO.2013.53.2473
15. Ciliberto D, Staropoli N, Caglioti F, et al. The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis. Crit Rev Oncol Hematol. 2018;125:69-77. DOI:10.1016/j.critrevonc.2018.03.003
16. Cascinu S, Rosati G, Nasti G, et al.; GISCAD investigators. Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients. Eur J Cancer. 2017;83:106-15. DOI:10.1016/j.ejca.2017.06.029
17. Xu J, Xu RH, Qin S, et al. Regorafenib in Chinese patients with metastatic colorectal cancer: Subgroup analysis of the phase 3 CONCUR trial. J Gastroenterol Hepatol. 2020;35(8):1307-16. DOI:10.1111/jgh.14974
18. Matsumoto T, Ikoma T, Yamamura S, et al. Regorafenib is suitable for advanced colorectal cancer patients who have previously received trifluridine/tipiracil plus bevacizumab. Sci Rep. 2023;13:2433. DOI:10.1038/s41598-023-29706-6
19. Федянин М.Ю., Трякин A.A., Тюляндин C.A. Метаанализ исследований по оценке эффективности продолжения применения антиангиогенных препаратов во 2-й линии терапии больных метастатическим раком толстой кишки в зависимости от мутационного статуса гена KRAS. Онкологическая колопроктология. 2018;8(2):38-45 [Fedyanin MYu, Tryakin AA, Tjulandin SA. Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: A meta-analysis. Onkologicheskaya Koloproktologiya = Colorectal Oncology. 2018;8(2):38-45 (in Russian)]. DOI:10.17650/2220-3478-2018-8-2-38-45
20. Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: An investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21(3):412-20. DOI:10.1016/S1470-2045(19)30827-7
21. Shitara K, Yamanaka T, Denda T, et al. REVERCE: A randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients. Ann Oncol. 2019;30(2):259-65. DOI:10.1093/annonc/mdy526
22. Cremolini C, Ciracì P, Pietrantonio F, et al. Panitumumab retreatment followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA (ctDNA): Results of the phase II randomized PARERE trial by GONO. J Clin Oncol. 2025;43:LBA3515-LBA3515. DOI:10.1200/JCO.2025.43.17_suppl.LBA3515
23. Vivas CS, Barrull JV, Rodriguez CF, et al. 511MO Third line rechallenge with cetuximab (Cet) and irinotecan in circulating tumor DNA (ctDNA) selected metastatic colorectal cancer (mCRC) patients: The randomized phase II CITRIC trial. Ann Oncol. 2024;35:S433-4. DOI:10.1016/j.annonc.2024.08.580
24. CITRIC Trial Results at ESMO 2025: ctDNA-Guided Anti-EGFR Rechallenge in Metastatic Colorectal Cancer. Available at: https://oncodaily.com/oncolibrary/citric-trial-colorectal-cancer-esmo25. Accessed: 05.08.2025.
25. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): A randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-79. DOI:10.1016/S1470-2045(14)70118-4
26. Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21(24):5469-79. DOI:10.1158/1078-0432.CCR-15-0526
27. Sakai D, Taniguchi H, Sugimoto N, et al. Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G). Eur J Cancer. 2020;135:11-21. DOI:10.1016/j.ejca.2020.04.014
28. Casadei-Gardini A, Vagheggini A, Gelsomino F, et al. Is there an optimal choice in refractory colorectal cancer? A network meta-analysis. Clin Colorectal Cancer. 2020;19(2):82-90.e9. DOI:10.1016/j.clcc.2019.10.001
29. Santini D, Vincenzi B, Addeo R, et al. Cetuximab rechallenge in metastatic colorectal cancer patients: How to come away from acquired resistance? Ann Oncol. 2012;23(9):2313-8. DOI:10.1093/annonc/mdr623. Erratum in: Ann Oncol. 2017;28(11):2906. DOI:10.1093/annonc/mdw551
30. Cremolini C, Rossini D, Dell’Aquila E, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: A phase 2 single-arm clinical trial. JAMA Oncol. 2019;5(3):343-50. DOI:10.1001/jamaoncol.2018.5080
2. Van Cutsem E, Martinelli E, Cascinu S, et al. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: Results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist. 2019;24(2):185-92. DOI:10.1634/theoncologist.2018-0072
3. Bekaii-Saab TS, Ou FS, Ahn DH. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): A randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070-82. DOI:10.1016/S1470-2045(19)30272-4
4. Lai E, Puzzoni M, Ziranu P, et al.; GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente, Italian Group for the Study of Gastrointestinal Tumors). Long term survival with regorafenib: REALITY (Real Life in Italy) Trial – A GISCAD study. Clin Colorectal Cancer. 2021;20(4):e253-62. DOI:10.1016/j.clcc.2021.07.008
5. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet. 2019;394(10207):1467-80. DOI:10.1016/S0140-6736(19)32319-0
6. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol. 2010;28(31):4697-705. DOI:10.1200/JCO.2009.27.4860
7. Rivera F, Karthaus M, Hecht JR, et al. Final analysis of the randomised PEAK trial: Overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017;32(8):1179-90. DOI:10.1007/s00384-017-2800-1
8. Watanabe J, Muro K, Shitara K, et al. Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial. JAMA. 2023;329(15):1271-82. DOI:10.1001/jama.2023.4428. Erratum in: JAMA. 2023;329(24):2196. DOI:10.1001/jama.2023.10533
9. Van Cutsem E, Lenz HJ, Köhne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33(7):692-700. DOI:10.1200/JCO.2014.59.4812
10. Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408-17. DOI:10.1056/NEJMoa0805019
11. Kuzmina ES, Fedyanin M, Lyadova MA, et al. Comparison of efficacy and safety of regorafenib and anti-EGFR targeted therapy in metastatic colorectal cancer: A retrospective study. Journal of Modern Oncology. 2024;26(3):341-7 (in Russian). DOI:10.26442/18151434.2024.3.202889
12. Salvatore L, Bensi M, Vivolo R, et al. Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients. Front Oncol. 2023;13:1125013. DOI:10.3389/fonc.2023.1125013
13. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-75. DOI:10.1016/S1470-2045(14)70330-4
14. Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240-7. DOI:10.1200/JCO.2013.53.2473
15. Ciliberto D, Staropoli N, Caglioti F, et al. The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis. Crit Rev Oncol Hematol. 2018;125:69-77. DOI:10.1016/j.critrevonc.2018.03.003
16. Cascinu S, Rosati G, Nasti G, et al.; GISCAD investigators. Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients. Eur J Cancer. 2017;83:106-15. DOI:10.1016/j.ejca.2017.06.029
17. Xu J, Xu RH, Qin S, et al. Regorafenib in Chinese patients with metastatic colorectal cancer: Subgroup analysis of the phase 3 CONCUR trial. J Gastroenterol Hepatol. 2020;35(8):1307-16. DOI:10.1111/jgh.14974
18. Matsumoto T, Ikoma T, Yamamura S, et al. Regorafenib is suitable for advanced colorectal cancer patients who have previously received trifluridine/tipiracil plus bevacizumab. Sci Rep. 2023;13:2433. DOI:10.1038/s41598-023-29706-6
19. Fedyanin MYu, Tryakin AA, Tjulandin SA. Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: A meta-analysis. Onkologicheskaya Koloproktologiya = Colorectal Oncology. 2018;8(2):38-45 (in Russian). DOI:10.17650/2220-3478-2018-8-2-38-45
20. Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: An investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21(3):412-20. DOI:10.1016/S1470-2045(19)30827-7
21. Shitara K, Yamanaka T, Denda T, et al. REVERCE: A randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients. Ann Oncol. 2019;30(2):259-65. DOI:10.1093/annonc/mdy526
22. Cremolini C, Ciracì P, Pietrantonio F, et al. Panitumumab retreatment followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA (ctDNA): Results of the phase II randomized PARERE trial by GONO. J Clin Oncol. 2025;43:LBA3515-LBA3515. DOI:10.1200/JCO.2025.43.17_suppl.LBA3515
23. Vivas CS, Barrull JV, Rodriguez CF, et al. 511MO Third line rechallenge with cetuximab (Cet) and irinotecan in circulating tumor DNA (ctDNA) selected metastatic colorectal cancer (mCRC) patients: The randomized phase II CITRIC trial. Ann Oncol. 2024;35:S433-4. DOI:10.1016/j.annonc.2024.08.580
24. CITRIC Trial Results at ESMO 2025: ctDNA-Guided Anti-EGFR Rechallenge in Metastatic Colorectal Cancer. Available at: https://oncodaily.com/oncolibrary/citric-trial-colorectal-cancer-esmo25. Accessed: 05.08.2025.
25. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): A randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-79. DOI:10.1016/S1470-2045(14)70118-4
26. Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21(24):5469-79. DOI:10.1158/1078-0432.CCR-15-0526
27. Sakai D, Taniguchi H, Sugimoto N, et al. Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G). Eur J Cancer. 2020;135:11-21. DOI:10.1016/j.ejca.2020.04.014
28. Casadei-Gardini A, Vagheggini A, Gelsomino F, et al. Is there an optimal choice in refractory colorectal cancer? A network meta-analysis. Clin Colorectal Cancer. 2020;19(2):82-90.e9. DOI:10.1016/j.clcc.2019.10.001
29. Santini D, Vincenzi B, Addeo R, et al. Cetuximab rechallenge in metastatic colorectal cancer patients: How to come away from acquired resistance? Ann Oncol. 2012;23(9):2313-8. DOI:10.1093/annonc/mdr623. Erratum in: Ann Oncol. 2017;28(11):2906. DOI:10.1093/annonc/mdw551
30. Cremolini C, Rossini D, Dell’Aquila E, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: A phase 2 single-arm clinical trial. JAMA Oncol. 2019;5(3):343-50. DOI:10.1001/jamaoncol.2018.5080
2. Van Cutsem E, Martinelli E, Cascinu S, et al. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: Results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist. 2019;24(2):185-92. DOI:10.1634/theoncologist.2018-0072
3. Bekaii-Saab TS, Ou FS, Ahn DH. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): A randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070-82. DOI:10.1016/S1470-2045(19)30272-4
4. Lai E, Puzzoni M, Ziranu P, et al.; GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente, Italian Group for the Study of Gastrointestinal Tumors). Long term survival with regorafenib: REALITY (Real Life in Italy) Trial – A GISCAD study. Clin Colorectal Cancer. 2021;20(4):e253-62. DOI:10.1016/j.clcc.2021.07.008
5. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet. 2019;394(10207):1467-80. DOI:10.1016/S0140-6736(19)32319-0
6. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol. 2010;28(31):4697-705. DOI:10.1200/JCO.2009.27.4860
7. Rivera F, Karthaus M, Hecht JR, et al. Final analysis of the randomised PEAK trial: Overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017;32(8):1179-90. DOI:10.1007/s00384-017-2800-1
8. Watanabe J, Muro K, Shitara K, et al. Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial. JAMA. 2023;329(15):1271-82. DOI:10.1001/jama.2023.4428. Erratum in: JAMA. 2023;329(24):2196. DOI:10.1001/jama.2023.10533
9. Van Cutsem E, Lenz HJ, Köhne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33(7):692-700. DOI:10.1200/JCO.2014.59.4812
10. Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408-17. DOI:10.1056/NEJMoa0805019
11. Кузьмина Е.С., Федянин М.Ю., Лядова М.А., и др. Сравнение эффективности и безопасности терапии регорафенибом и анти-EGFR таргетной терапии при метастатическом колоректальном раке. Современная Онкология. 2024;26(3):341-7 [Kuzmina ES, Fedyanin M, Lyadova MA, et al. Comparison of efficacy and safety of regorafenib and anti-EGFR targeted therapy in metastatic colorectal cancer: A retrospective study. Journal of Modern Oncology. 2024;26(3):341-7 (in Russian)]. DOI:10.26442/18151434.2024.3.202889
12. Salvatore L, Bensi M, Vivolo R, et al. Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients. Front Oncol. 2023;13:1125013. DOI:10.3389/fonc.2023.1125013
13. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-75. DOI:10.1016/S1470-2045(14)70330-4
14. Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240-7. DOI:10.1200/JCO.2013.53.2473
15. Ciliberto D, Staropoli N, Caglioti F, et al. The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis. Crit Rev Oncol Hematol. 2018;125:69-77. DOI:10.1016/j.critrevonc.2018.03.003
16. Cascinu S, Rosati G, Nasti G, et al.; GISCAD investigators. Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients. Eur J Cancer. 2017;83:106-15. DOI:10.1016/j.ejca.2017.06.029
17. Xu J, Xu RH, Qin S, et al. Regorafenib in Chinese patients with metastatic colorectal cancer: Subgroup analysis of the phase 3 CONCUR trial. J Gastroenterol Hepatol. 2020;35(8):1307-16. DOI:10.1111/jgh.14974
18. Matsumoto T, Ikoma T, Yamamura S, et al. Regorafenib is suitable for advanced colorectal cancer patients who have previously received trifluridine/tipiracil plus bevacizumab. Sci Rep. 2023;13:2433. DOI:10.1038/s41598-023-29706-6
19. Федянин М.Ю., Трякин A.A., Тюляндин C.A. Метаанализ исследований по оценке эффективности продолжения применения антиангиогенных препаратов во 2-й линии терапии больных метастатическим раком толстой кишки в зависимости от мутационного статуса гена KRAS. Онкологическая колопроктология. 2018;8(2):38-45 [Fedyanin MYu, Tryakin AA, Tjulandin SA. Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: A meta-analysis. Onkologicheskaya Koloproktologiya = Colorectal Oncology. 2018;8(2):38-45 (in Russian)]. DOI:10.17650/2220-3478-2018-8-2-38-45
20. Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: An investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21(3):412-20. DOI:10.1016/S1470-2045(19)30827-7
21. Shitara K, Yamanaka T, Denda T, et al. REVERCE: A randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients. Ann Oncol. 2019;30(2):259-65. DOI:10.1093/annonc/mdy526
22. Cremolini C, Ciracì P, Pietrantonio F, et al. Panitumumab retreatment followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA (ctDNA): Results of the phase II randomized PARERE trial by GONO. J Clin Oncol. 2025;43:LBA3515-LBA3515. DOI:10.1200/JCO.2025.43.17_suppl.LBA3515
23. Vivas CS, Barrull JV, Rodriguez CF, et al. 511MO Third line rechallenge with cetuximab (Cet) and irinotecan in circulating tumor DNA (ctDNA) selected metastatic colorectal cancer (mCRC) patients: The randomized phase II CITRIC trial. Ann Oncol. 2024;35:S433-4. DOI:10.1016/j.annonc.2024.08.580
24. CITRIC Trial Results at ESMO 2025: ctDNA-Guided Anti-EGFR Rechallenge in Metastatic Colorectal Cancer. Available at: https://oncodaily.com/oncolibrary/citric-trial-colorectal-cancer-esmo25. Accessed: 05.08.2025.
25. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): A randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-79. DOI:10.1016/S1470-2045(14)70118-4
26. Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21(24):5469-79. DOI:10.1158/1078-0432.CCR-15-0526
27. Sakai D, Taniguchi H, Sugimoto N, et al. Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G). Eur J Cancer. 2020;135:11-21. DOI:10.1016/j.ejca.2020.04.014
28. Casadei-Gardini A, Vagheggini A, Gelsomino F, et al. Is there an optimal choice in refractory colorectal cancer? A network meta-analysis. Clin Colorectal Cancer. 2020;19(2):82-90.e9. DOI:10.1016/j.clcc.2019.10.001
29. Santini D, Vincenzi B, Addeo R, et al. Cetuximab rechallenge in metastatic colorectal cancer patients: How to come away from acquired resistance? Ann Oncol. 2012;23(9):2313-8. DOI:10.1093/annonc/mdr623. Erratum in: Ann Oncol. 2017;28(11):2906. DOI:10.1093/annonc/mdw551
30. Cremolini C, Rossini D, Dell’Aquila E, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: A phase 2 single-arm clinical trial. JAMA Oncol. 2019;5(3):343-50. DOI:10.1001/jamaoncol.2018.5080
________________________________________________
2. Van Cutsem E, Martinelli E, Cascinu S, et al. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: Results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist. 2019;24(2):185-92. DOI:10.1634/theoncologist.2018-0072
3. Bekaii-Saab TS, Ou FS, Ahn DH. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): A randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070-82. DOI:10.1016/S1470-2045(19)30272-4
4. Lai E, Puzzoni M, Ziranu P, et al.; GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente, Italian Group for the Study of Gastrointestinal Tumors). Long term survival with regorafenib: REALITY (Real Life in Italy) Trial – A GISCAD study. Clin Colorectal Cancer. 2021;20(4):e253-62. DOI:10.1016/j.clcc.2021.07.008
5. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet. 2019;394(10207):1467-80. DOI:10.1016/S0140-6736(19)32319-0
6. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol. 2010;28(31):4697-705. DOI:10.1200/JCO.2009.27.4860
7. Rivera F, Karthaus M, Hecht JR, et al. Final analysis of the randomised PEAK trial: Overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017;32(8):1179-90. DOI:10.1007/s00384-017-2800-1
8. Watanabe J, Muro K, Shitara K, et al. Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial. JAMA. 2023;329(15):1271-82. DOI:10.1001/jama.2023.4428. Erratum in: JAMA. 2023;329(24):2196. DOI:10.1001/jama.2023.10533
9. Van Cutsem E, Lenz HJ, Köhne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33(7):692-700. DOI:10.1200/JCO.2014.59.4812
10. Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408-17. DOI:10.1056/NEJMoa0805019
11. Kuzmina ES, Fedyanin M, Lyadova MA, et al. Comparison of efficacy and safety of regorafenib and anti-EGFR targeted therapy in metastatic colorectal cancer: A retrospective study. Journal of Modern Oncology. 2024;26(3):341-7 (in Russian). DOI:10.26442/18151434.2024.3.202889
12. Salvatore L, Bensi M, Vivolo R, et al. Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients. Front Oncol. 2023;13:1125013. DOI:10.3389/fonc.2023.1125013
13. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-75. DOI:10.1016/S1470-2045(14)70330-4
14. Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240-7. DOI:10.1200/JCO.2013.53.2473
15. Ciliberto D, Staropoli N, Caglioti F, et al. The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis. Crit Rev Oncol Hematol. 2018;125:69-77. DOI:10.1016/j.critrevonc.2018.03.003
16. Cascinu S, Rosati G, Nasti G, et al.; GISCAD investigators. Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients. Eur J Cancer. 2017;83:106-15. DOI:10.1016/j.ejca.2017.06.029
17. Xu J, Xu RH, Qin S, et al. Regorafenib in Chinese patients with metastatic colorectal cancer: Subgroup analysis of the phase 3 CONCUR trial. J Gastroenterol Hepatol. 2020;35(8):1307-16. DOI:10.1111/jgh.14974
18. Matsumoto T, Ikoma T, Yamamura S, et al. Regorafenib is suitable for advanced colorectal cancer patients who have previously received trifluridine/tipiracil plus bevacizumab. Sci Rep. 2023;13:2433. DOI:10.1038/s41598-023-29706-6
19. Fedyanin MYu, Tryakin AA, Tjulandin SA. Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: A meta-analysis. Onkologicheskaya Koloproktologiya = Colorectal Oncology. 2018;8(2):38-45 (in Russian). DOI:10.17650/2220-3478-2018-8-2-38-45
20. Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: An investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21(3):412-20. DOI:10.1016/S1470-2045(19)30827-7
21. Shitara K, Yamanaka T, Denda T, et al. REVERCE: A randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients. Ann Oncol. 2019;30(2):259-65. DOI:10.1093/annonc/mdy526
22. Cremolini C, Ciracì P, Pietrantonio F, et al. Panitumumab retreatment followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA (ctDNA): Results of the phase II randomized PARERE trial by GONO. J Clin Oncol. 2025;43:LBA3515-LBA3515. DOI:10.1200/JCO.2025.43.17_suppl.LBA3515
23. Vivas CS, Barrull JV, Rodriguez CF, et al. 511MO Third line rechallenge with cetuximab (Cet) and irinotecan in circulating tumor DNA (ctDNA) selected metastatic colorectal cancer (mCRC) patients: The randomized phase II CITRIC trial. Ann Oncol. 2024;35:S433-4. DOI:10.1016/j.annonc.2024.08.580
24. CITRIC Trial Results at ESMO 2025: ctDNA-Guided Anti-EGFR Rechallenge in Metastatic Colorectal Cancer. Available at: https://oncodaily.com/oncolibrary/citric-trial-colorectal-cancer-esmo25. Accessed: 05.08.2025.
25. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): A randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-79. DOI:10.1016/S1470-2045(14)70118-4
26. Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21(24):5469-79. DOI:10.1158/1078-0432.CCR-15-0526
27. Sakai D, Taniguchi H, Sugimoto N, et al. Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G). Eur J Cancer. 2020;135:11-21. DOI:10.1016/j.ejca.2020.04.014
28. Casadei-Gardini A, Vagheggini A, Gelsomino F, et al. Is there an optimal choice in refractory colorectal cancer? A network meta-analysis. Clin Colorectal Cancer. 2020;19(2):82-90.e9. DOI:10.1016/j.clcc.2019.10.001
29. Santini D, Vincenzi B, Addeo R, et al. Cetuximab rechallenge in metastatic colorectal cancer patients: How to come away from acquired resistance? Ann Oncol. 2012;23(9):2313-8. DOI:10.1093/annonc/mdr623. Erratum in: Ann Oncol. 2017;28(11):2906. DOI:10.1093/annonc/mdw551
30. Cremolini C, Rossini D, Dell’Aquila E, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: A phase 2 single-arm clinical trial. JAMA Oncol. 2019;5(3):343-50. DOI:10.1001/jamaoncol.2018.5080
Авторы
Е.С. Кузьмина*1, М.Ю. Федянин2–4, П.С. Феоктистова5,6, М.А. Лядова1,7, Д.С. Федоринов4,8,9, О.Р. Магамедова5, С.А. Партс1,10, М.А. Полянский1, Е.П. Фехтел1, И.А. Покатаев1, М.А. Осипов11, А.А. Дацюк12, Н.П. Беляк13,14, Р.В. Орлова13,14, Е.А. Мгарь14, В.М. Кузьмин15, Е.В. Глазкова4, Т.Г. Антонова1, В.Н. Галкин1
1ГБУЗ г. Москвы «Городская клиническая больница им. С.С. Юдина Департамента здравоохранения г. Москвы», Москва, Российская Федерация
2ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Российская Федерация
3ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, Москва, Российская Федерация
4ГБУЗ «Московский многопрофильный клинический центр "Коммунарка"» Департамента здравоохранения г. Москвы, Москва, Российская Федерация
5ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Российская Федерация
6ФГБОУ ВО «Российский университет медицины» Минздрава России, Москва, Российская Федерация
7Новокузнецкий государственный институт усовершенствования врачей – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Новокузнецк, Российская Федерация
8ФГБНУ «Российский научный центр хирургии им. акад. Б.В. Петровского», Москва, Российская Федерация
9ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Российская Федерация
10ФГБУ «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий» ФМБА России, Москва, Российская Федерация
11ГБУЗ «Ленинградская областная клиническая больница», Санкт-Петербург, Российская Федерация
12ГАУЗ НО «Научно-исследовательский институт клинической онкологии "Нижегородский областной клинический онкологический диспансер"», Нижний Новгород, Российская Федерация
13ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Российская Федерация
14СПб ГБУЗ «Городской клинический онкологический диспансер», Санкт-Петербург, Российская Федерация
15ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Российская Федерация
*kuz011@mail.ru
1Moscow State Budgetary Healthcare Institution «Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department», Moscow, Russian Federation
2Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
3Pirogov National Medical and Surgical Center, Moscow, Russian Federation
4Moscow Multidisciplinary Clinical Center “Kommunarka”, Moscow, Russian Federation
5Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation
6Russian University of Medicine, Moscow, Russian Federation
7Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Novokuznetsk, Russian Federation
8Petrovskiy Russian Research Center of Surgery, Moscow, Russian Federation
9Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation
10Federal Research and Clinical Center of Specialized Types of Health Care and Medical Technology, Moscow, Russian Federation
11Leningrad Regional Clinical Hospital, Saint Petersburg, Russian Federation
12Research Institute of Clinical Oncology "Nizhny Novgorod Regional Clinical Oncological Dispensary", Nizhny Novgorod, Russian Federation
13Saint Petersburg State University, Saint Petersburg, Russian Federation
14City Clinical Oncological Dispensary, Saint Petersburg, Russian Federation
15Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
*kuz011@mail.ru
1ГБУЗ г. Москвы «Городская клиническая больница им. С.С. Юдина Департамента здравоохранения г. Москвы», Москва, Российская Федерация
2ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Российская Федерация
3ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, Москва, Российская Федерация
4ГБУЗ «Московский многопрофильный клинический центр "Коммунарка"» Департамента здравоохранения г. Москвы, Москва, Российская Федерация
5ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Российская Федерация
6ФГБОУ ВО «Российский университет медицины» Минздрава России, Москва, Российская Федерация
7Новокузнецкий государственный институт усовершенствования врачей – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Новокузнецк, Российская Федерация
8ФГБНУ «Российский научный центр хирургии им. акад. Б.В. Петровского», Москва, Российская Федерация
9ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Российская Федерация
10ФГБУ «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий» ФМБА России, Москва, Российская Федерация
11ГБУЗ «Ленинградская областная клиническая больница», Санкт-Петербург, Российская Федерация
12ГАУЗ НО «Научно-исследовательский институт клинической онкологии "Нижегородский областной клинический онкологический диспансер"», Нижний Новгород, Российская Федерация
13ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Российская Федерация
14СПб ГБУЗ «Городской клинический онкологический диспансер», Санкт-Петербург, Российская Федерация
15ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Российская Федерация
*kuz011@mail.ru
________________________________________________
1Moscow State Budgetary Healthcare Institution «Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department», Moscow, Russian Federation
2Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
3Pirogov National Medical and Surgical Center, Moscow, Russian Federation
4Moscow Multidisciplinary Clinical Center “Kommunarka”, Moscow, Russian Federation
5Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation
6Russian University of Medicine, Moscow, Russian Federation
7Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Novokuznetsk, Russian Federation
8Petrovskiy Russian Research Center of Surgery, Moscow, Russian Federation
9Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation
10Federal Research and Clinical Center of Specialized Types of Health Care and Medical Technology, Moscow, Russian Federation
11Leningrad Regional Clinical Hospital, Saint Petersburg, Russian Federation
12Research Institute of Clinical Oncology "Nizhny Novgorod Regional Clinical Oncological Dispensary", Nizhny Novgorod, Russian Federation
13Saint Petersburg State University, Saint Petersburg, Russian Federation
14City Clinical Oncological Dispensary, Saint Petersburg, Russian Federation
15Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
*kuz011@mail.ru
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