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Регорафениб: от клинических исследований до клинической практики
Регорафениб: от клинических исследований до клинической практики
Федянин М.Ю., Трякин А.А. Регорафениб: от клинических исследований до клинической практики. Современная Онкология. 2017; 19 (3): 19–24.
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Аннотация
Регорафениб – новый мультитирозинкиназный ингибитор с противоопухолевой и антиангиогенной активностью, недавно одобрен к применению в Российской Федерации при колоректальном раке, гастроинтестиальных опухолях. Ожидается его регистрация и при гепатоцеллюлярном раке. В данном обзоре рассмотрены основные клинические исследования препарата, особенности назначения, профилактики и лечения осложнений новым тирозинкиназным ингибитором, мнения зарубежных и российских экспертов, которые должны помочь химиотерапевту в его клинической практике.
Ключевые слова: регорафениб, колоректальный рак, гастроинтестинальная опухоль, гепатоцеллюлярный рак.
Key words: regorafenib, colon cancer, gastrointestinal tumor, hepatocellular carcinoma.
Ключевые слова: регорафениб, колоректальный рак, гастроинтестинальная опухоль, гепатоцеллюлярный рак.
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Key words: regorafenib, colon cancer, gastrointestinal tumor, hepatocellular carcinoma.
Полный текст
Список литературы
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4. Mross K, Frost A, Steinbild S et al. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012; 18 (9): 2658–67.
5. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12.
6. Li J, Qin S, Xu R et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619–29.
7. Adenis A, de la Fouchardiere C, Paule B et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 2016; 16: 412.
8. De la Fouchardiere C, Paule B, Burtin P et al. Survival benefit, safety, and prognostic factors for outcome with Regorafenib (REG) in patients (pts) with pretreated metastatic colorectal cancer (mCRC). Main analyses of the REBECCA study. Abstract 2095. ESMO 17th World Congress on Gastrointestinal Cancer, 1–4 July, 2015.
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11. Komatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). Abstract 680. 2016 Gastrointestinal Cancers Symposium, San Francisco, California, USA, 21–23 January 2016.
12. Argileґs G, Saunders MP, Rivera F et al. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial. Eur J Cancer 2015; 51: 942–9.
13. Schultheis B, Folprecht G, Kuhlmann J et al. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol 2013; 24 (6): 1560–7.
14. O’Neil B, O'Reilly S, Kasbari S et al. A multi-center, randomized, double-blind phase II trial of FOLFIRI + regorafenib or placebo for patients with metastatic colorectal cancer who failed one prior line of oxaliplatin containing therapy. Abstract 464P. Ann Oncol 2016; 27 (6): 149–206.
15. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (correct): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12.
16. Garcia-Carbonero R, Van Cutsem E, Ciardiello F et al. Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the phase 3b CONSIGN trial who had progression-free survival (PFS) >4 months (m). Ann Oncol 2016; 27, Issue (Suppl. 6): 506.
17. Grothey A, Falcone A, Humblet Y et al. Characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) who had progression-free survival (PFS) >4 months (m): Subgroup analysis of the phase 3 CORRECT trial. Ann Oncol 2016; 27, Issue (Suppl. 6): 516.
18. Ricotta R, Sartore-Bianchi A, Verrioli A et al. Regorafenib for metastatic colorectal cancer. Lancet 2013; 381 (9877): 1537.
19. Prete Michela D, Scartozzi M, Prochilo T et al. LDH serum levels as a predictive factor for global outcome in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management. J Clin Oncol 2014; 32 (3), Suppl.: 497.
20. Komori A, Taniguchi H, Kito Y et al. Serum CA19-9 response is an early predictive marker for the efficacy of regorafenib in refractory metastatic colorectal cancer. Ann Oncol 2015; 26, Issue (Suppl. 9): ix51–ix52.
21. Grothey A, Huang L, Wagner A et al. Hand-foot skin reaction (HFSR) and outcomes in the phase 3 CORRECT trial of regorafenib for metastatic colorectal cancer (mCRC). ASCO2017; abst. 3551.
22. Kmatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). ASCO GI 2017, abst. 680.
23. Bruix J et al. Updated overall survival (OS) analysis from the international, phase 3, randomized, placebo-controlled RESORCE trial of regorafenib for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. World GI conference 2017, abs. O-009.
24. De Jesus-Gonzalez N, Robinson E, Penchev R et al. Regorafenib induces rapid and reversible changes in plasma nitric oxide and endothelin-1. Am J Hypertens 2012; 25 (10): 1118–23.
25. Tabernero J, Lenz HJ, Siena S et al. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. CORRECT trial. Lancet Oncol 2015; 16 (8): 937–48.
26. Giampieri R, Salvatore L, Del Prete M et al. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients. ASCO Meeting Abstr 2015; 33 (Suppl. 3): 595.
27. Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013;10(5):e1001453.
28. Teufel M, Schwenke S, Seidel H et al. Molecular subtypes and outcomes in regorafenib-treated patients with metastatic colorectal cancer (mCRC) enrolled in the CORRECT trial. ASCO Meeting Abstracts 2015; 33 (Suppl. 15): 3558.
29. Rechsteiner M, Wild P, Kiessling MK et al. A novel germline mutation of PDGFR-b might be associated with clinical response of colorectal cancer to regorafenib. Ann Oncol 2015; 26 (1): 246–8с.
30. Guida T, Anaganti S, Provitera L et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res 2007; 13: 3363–9.
31. Loaiza-Bonilla A, Jensen CE, Shroff S et al. KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer. Cureus 2016; 8 (2): e478.
32. Kang HJ, Koh KH, Yang E et al. Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations. Proteomics 2006; 6: 11517.
33. Rajendra R, Pollack SM, Jones RL. Management of gastrointestinal stromal tumors. Future Oncol 2013; 9: 193206.
34. Blanke CD, Rankin C, Demetri GD et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008; 26 (4): 626–32.
35. Demetri GD, Reichardt P, Kang YK et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381 (9863): 295–302.
36. Maleddu A, Pantaleo MA, Nannini M et al. Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncol Rep 2009; 21: 1359–66.
37. Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev 2007; 17: 3–7.
38. Heinrich MC, Maki RG, Corless CL et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26: 5352–9.
39. Gounder MM, Maki RG. Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor. Cancer Chem Pharm 2011; 67 (Suppl. 1): S25–S43.
40. George S, von Mehren M, Heinrich MC et al. A multicenter phase II study of regorafenib in patients with advanced gastrointestinal stromal tumor after therapy with imatinib and sunitinib. J Clin Oncol 2011; 29: 10007.
41. Cheng AL, Kang YK, Lin DY et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067–75.
42. Cheng A-L, Finn RS, Qin S. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). J Clin Oncol 2017; 35 (15). Suppl.: 4001.
43. Bruix J, Merle P, Granito A et al. Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial (abstract LBA-03). Ann Oncol 2016; 27 (Suppl. 2): ii140–ii141.
44. Kudo M. Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016; 5: 235–44.
45. A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib. Liver Cancer 2017; 6 (3): 177–84.
46. Bruix J et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J Hepatol 2012; 57, Issue 4: 821–9.
2. Wilhelm SM, Dumas J, Adnane L et al. Regorafenib (BAY 73-4506):
a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011;129 (1): 245–55.
3. Carr BI, D`Alessandro R, Refolo MG et al. Effect of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro. J Cell Physiol 2013; 228 (6): 1244–350.
4. Mross K, Frost A, Steinbild S et al. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012; 18 (9): 2658–67.
5. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12.
6. Li J, Qin S, Xu R et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619–29.
7. Adenis A, de la Fouchardiere C, Paule B et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 2016; 16: 412.
8. De la Fouchardiere C, Paule B, Burtin P et al. Survival benefit, safety, and prognostic factors for outcome with Regorafenib (REG) in patients (pts) with pretreated metastatic colorectal cancer (mCRC). Main analyses of the REBECCA study. Abstract 2095. ESMO 17th World Congress on Gastrointestinal Cancer, 1–4 July, 2015.
9. Van Cutsem E, Ciardiello F, Seitz J-F et al. Results from the large, open-label phase 3b CONSIGN study of regorafenib in patients with previously treated metastatic colorectal cancer. Ann Oncol 26 (Suppl. 4): iv118-iv118.
10. Van Cutsem E, Ciardiello F, Ychou M et al. Regorafenib in previously treated metastatic colorectal cancer (mCRC): Analysis of age subgroups in the open-label phase IIIb CONSIGN trial. Abstract 3524. ASCO Annual Meeting, 3–7 June, 2016.
11. Komatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). Abstract 680. 2016 Gastrointestinal Cancers Symposium, San Francisco, California, USA, 21–23 January 2016.
12. Argileґs G, Saunders MP, Rivera F et al. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial. Eur J Cancer 2015; 51: 942–9.
13. Schultheis B, Folprecht G, Kuhlmann J et al. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol 2013; 24 (6): 1560–7.
14. O’Neil B, O'Reilly S, Kasbari S et al. A multi-center, randomized, double-blind phase II trial of FOLFIRI + regorafenib or placebo for patients with metastatic colorectal cancer who failed one prior line of oxaliplatin containing therapy. Abstract 464P. Ann Oncol 2016; 27 (6): 149–206.
15. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (correct): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12.
16. Garcia-Carbonero R, Van Cutsem E, Ciardiello F et al. Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the phase 3b CONSIGN trial who had progression-free survival (PFS) >4 months (m). Ann Oncol 2016; 27, Issue (Suppl. 6): 506.
17. Grothey A, Falcone A, Humblet Y et al. Characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) who had progression-free survival (PFS) >4 months (m): Subgroup analysis of the phase 3 CORRECT trial. Ann Oncol 2016; 27, Issue (Suppl. 6): 516.
18. Ricotta R, Sartore-Bianchi A, Verrioli A et al. Regorafenib for metastatic colorectal cancer. Lancet 2013; 381 (9877): 1537.
19. Prete Michela D, Scartozzi M, Prochilo T et al. LDH serum levels as a predictive factor for global outcome in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management. J Clin Oncol 2014; 32 (3), Suppl.: 497.
20. Komori A, Taniguchi H, Kito Y et al. Serum CA19-9 response is an early predictive marker for the efficacy of regorafenib in refractory metastatic colorectal cancer. Ann Oncol 2015; 26, Issue (Suppl. 9): ix51–ix52.
21. Grothey A, Huang L, Wagner A et al. Hand-foot skin reaction (HFSR) and outcomes in the phase 3 CORRECT trial of regorafenib for metastatic colorectal cancer (mCRC). ASCO2017; abst. 3551.
22. Kmatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). ASCO GI 2017, abst. 680.
23. Bruix J et al. Updated overall survival (OS) analysis from the international, phase 3, randomized, placebo-controlled RESORCE trial of regorafenib for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. World GI conference 2017, abs. O-009.
24. De Jesus-Gonzalez N, Robinson E, Penchev R et al. Regorafenib induces rapid and reversible changes in plasma nitric oxide and endothelin-1. Am J Hypertens 2012; 25 (10): 1118–23.
25. Tabernero J, Lenz HJ, Siena S et al. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. CORRECT trial. Lancet Oncol 2015; 16 (8): 937–48.
26. Giampieri R, Salvatore L, Del Prete M et al. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients. ASCO Meeting Abstr 2015; 33 (Suppl. 3): 595.
27. Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013;10(5):e1001453.
28. Teufel M, Schwenke S, Seidel H et al. Molecular subtypes and outcomes in regorafenib-treated patients with metastatic colorectal cancer (mCRC) enrolled in the CORRECT trial. ASCO Meeting Abstracts 2015; 33 (Suppl. 15): 3558.
29. Rechsteiner M, Wild P, Kiessling MK et al. A novel germline mutation of PDGFR-b might be associated with clinical response of colorectal cancer to regorafenib. Ann Oncol 2015; 26 (1): 246–8с.
30. Guida T, Anaganti S, Provitera L et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res 2007; 13: 3363–9.
31. Loaiza-Bonilla A, Jensen CE, Shroff S et al. KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer. Cureus 2016; 8 (2): e478.
32. Kang HJ, Koh KH, Yang E et al. Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations. Proteomics 2006; 6: 11517.
33. Rajendra R, Pollack SM, Jones RL. Management of gastrointestinal stromal tumors. Future Oncol 2013; 9: 193206.
34. Blanke CD, Rankin C, Demetri GD et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008; 26 (4): 626–32.
35. Demetri GD, Reichardt P, Kang YK et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381 (9863): 295–302.
36. Maleddu A, Pantaleo MA, Nannini M et al. Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncol Rep 2009; 21: 1359–66.
37. Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev 2007; 17: 3–7.
38. Heinrich MC, Maki RG, Corless CL et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26: 5352–9.
39. Gounder MM, Maki RG. Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor. Cancer Chem Pharm 2011; 67 (Suppl. 1): S25–S43.
40. George S, von Mehren M, Heinrich MC et al. A multicenter phase II study of regorafenib in patients with advanced gastrointestinal stromal tumor after therapy with imatinib and sunitinib. J Clin Oncol 2011; 29: 10007.
41. Cheng AL, Kang YK, Lin DY et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067–75.
42. Cheng A-L, Finn RS, Qin S. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). J Clin Oncol 2017; 35 (15). Suppl.: 4001.
43. Bruix J, Merle P, Granito A et al. Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial (abstract LBA-03). Ann Oncol 2016; 27 (Suppl. 2): ii140–ii141.
44. Kudo M. Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016; 5: 235–44.
45. A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib. Liver Cancer 2017; 6 (3): 177–84.
46. Bruix J et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J Hepatol 2012; 57, Issue 4: 821–9.
2. Wilhelm SM, Dumas J, Adnane L et al. Regorafenib (BAY 73-4506):
a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011;129 (1): 245–55.
3. Carr BI, D`Alessandro R, Refolo MG et al. Effect of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro. J Cell Physiol 2013; 228 (6): 1244–350.
4. Mross K, Frost A, Steinbild S et al. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012; 18 (9): 2658–67.
5. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12.
6. Li J, Qin S, Xu R et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619–29.
7. Adenis A, de la Fouchardiere C, Paule B et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 2016; 16: 412.
8. De la Fouchardiere C, Paule B, Burtin P et al. Survival benefit, safety, and prognostic factors for outcome with Regorafenib (REG) in patients (pts) with pretreated metastatic colorectal cancer (mCRC). Main analyses of the REBECCA study. Abstract 2095. ESMO 17th World Congress on Gastrointestinal Cancer, 1–4 July, 2015.
9. Van Cutsem E, Ciardiello F, Seitz J-F et al. Results from the large, open-label phase 3b CONSIGN study of regorafenib in patients with previously treated metastatic colorectal cancer. Ann Oncol 26 (Suppl. 4): iv118-iv118.
10. Van Cutsem E, Ciardiello F, Ychou M et al. Regorafenib in previously treated metastatic colorectal cancer (mCRC): Analysis of age subgroups in the open-label phase IIIb CONSIGN trial. Abstract 3524. ASCO Annual Meeting, 3–7 June, 2016.
11. Komatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). Abstract 680. 2016 Gastrointestinal Cancers Symposium, San Francisco, California, USA, 21–23 January 2016.
12. Argileґs G, Saunders MP, Rivera F et al. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial. Eur J Cancer 2015; 51: 942–9.
13. Schultheis B, Folprecht G, Kuhlmann J et al. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol 2013; 24 (6): 1560–7.
14. O’Neil B, O'Reilly S, Kasbari S et al. A multi-center, randomized, double-blind phase II trial of FOLFIRI + regorafenib or placebo for patients with metastatic colorectal cancer who failed one prior line of oxaliplatin containing therapy. Abstract 464P. Ann Oncol 2016; 27 (6): 149–206.
15. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (correct): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12.
16. Garcia-Carbonero R, Van Cutsem E, Ciardiello F et al. Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the phase 3b CONSIGN trial who had progression-free survival (PFS) >4 months (m). Ann Oncol 2016; 27, Issue (Suppl. 6): 506.
17. Grothey A, Falcone A, Humblet Y et al. Characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) who had progression-free survival (PFS) >4 months (m): Subgroup analysis of the phase 3 CORRECT trial. Ann Oncol 2016; 27, Issue (Suppl. 6): 516.
18. Ricotta R, Sartore-Bianchi A, Verrioli A et al. Regorafenib for metastatic colorectal cancer. Lancet 2013; 381 (9877): 1537.
19. Prete Michela D, Scartozzi M, Prochilo T et al. LDH serum levels as a predictive factor for global outcome in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management. J Clin Oncol 2014; 32 (3), Suppl.: 497.
20. Komori A, Taniguchi H, Kito Y et al. Serum CA19-9 response is an early predictive marker for the efficacy of regorafenib in refractory metastatic colorectal cancer. Ann Oncol 2015; 26, Issue (Suppl. 9): ix51–ix52.
21. Grothey A, Huang L, Wagner A et al. Hand-foot skin reaction (HFSR) and outcomes in the phase 3 CORRECT trial of regorafenib for metastatic colorectal cancer (mCRC). ASCO2017; abst. 3551.
22. Kmatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). ASCO GI 2017, abst. 680.
23. Bruix J et al. Updated overall survival (OS) analysis from the international, phase 3, randomized, placebo-controlled RESORCE trial of regorafenib for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. World GI conference 2017, abs. O-009.
24. De Jesus-Gonzalez N, Robinson E, Penchev R et al. Regorafenib induces rapid and reversible changes in plasma nitric oxide and endothelin-1. Am J Hypertens 2012; 25 (10): 1118–23.
25. Tabernero J, Lenz HJ, Siena S et al. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. CORRECT trial. Lancet Oncol 2015; 16 (8): 937–48.
26. Giampieri R, Salvatore L, Del Prete M et al. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients. ASCO Meeting Abstr 2015; 33 (Suppl. 3): 595.
27. Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013;10(5):e1001453.
28. Teufel M, Schwenke S, Seidel H et al. Molecular subtypes and outcomes in regorafenib-treated patients with metastatic colorectal cancer (mCRC) enrolled in the CORRECT trial. ASCO Meeting Abstracts 2015; 33 (Suppl. 15): 3558.
29. Rechsteiner M, Wild P, Kiessling MK et al. A novel germline mutation of PDGFR-b might be associated with clinical response of colorectal cancer to regorafenib. Ann Oncol 2015; 26 (1): 246–8с.
30. Guida T, Anaganti S, Provitera L et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res 2007; 13: 3363–9.
31. Loaiza-Bonilla A, Jensen CE, Shroff S et al. KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer. Cureus 2016; 8 (2): e478.
32. Kang HJ, Koh KH, Yang E et al. Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations. Proteomics 2006; 6: 11517.
33. Rajendra R, Pollack SM, Jones RL. Management of gastrointestinal stromal tumors. Future Oncol 2013; 9: 193206.
34. Blanke CD, Rankin C, Demetri GD et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008; 26 (4): 626–32.
35. Demetri GD, Reichardt P, Kang YK et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381 (9863): 295–302.
36. Maleddu A, Pantaleo MA, Nannini M et al. Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncol Rep 2009; 21: 1359–66.
37. Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev 2007; 17: 3–7.
38. Heinrich MC, Maki RG, Corless CL et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26: 5352–9.
39. Gounder MM, Maki RG. Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor. Cancer Chem Pharm 2011; 67 (Suppl. 1): S25–S43.
40. George S, von Mehren M, Heinrich MC et al. A multicenter phase II study of regorafenib in patients with advanced gastrointestinal stromal tumor after therapy with imatinib and sunitinib. J Clin Oncol 2011; 29: 10007.
41. Cheng AL, Kang YK, Lin DY et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067–75.
42. Cheng A-L, Finn RS, Qin S. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). J Clin Oncol 2017; 35 (15). Suppl.: 4001.
43. Bruix J, Merle P, Granito A et al. Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial (abstract LBA-03). Ann Oncol 2016; 27 (Suppl. 2): ii140–ii141.
44. Kudo M. Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016; 5: 235–44.
45. A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib. Liver Cancer 2017; 6 (3): 177–84.
46. Bruix J et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J Hepatol 2012; 57, Issue 4: 821–9.
________________________________________________
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16. Garcia-Carbonero R, Van Cutsem E, Ciardiello F et al. Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the phase 3b CONSIGN trial who had progression-free survival (PFS) >4 months (m). Ann Oncol 2016; 27, Issue (Suppl. 6): 506.
17. Grothey A, Falcone A, Humblet Y et al. Characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) who had progression-free survival (PFS) >4 months (m): Subgroup analysis of the phase 3 CORRECT trial. Ann Oncol 2016; 27, Issue (Suppl. 6): 516.
18. Ricotta R, Sartore-Bianchi A, Verrioli A et al. Regorafenib for metastatic colorectal cancer. Lancet 2013; 381 (9877): 1537.
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21. Grothey A, Huang L, Wagner A et al. Hand-foot skin reaction (HFSR) and outcomes in the phase 3 CORRECT trial of regorafenib for metastatic colorectal cancer (mCRC). ASCO2017; abst. 3551.
22. Kmatsu Y, Muro K, Yamaguchi K et al. Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS). ASCO GI 2017, abst. 680.
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25. Tabernero J, Lenz HJ, Siena S et al. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. CORRECT trial. Lancet Oncol 2015; 16 (8): 937–48.
26. Giampieri R, Salvatore L, Del Prete M et al. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients. ASCO Meeting Abstr 2015; 33 (Suppl. 3): 595.
27. Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013;10(5):e1001453.
28. Teufel M, Schwenke S, Seidel H et al. Molecular subtypes and outcomes in regorafenib-treated patients with metastatic colorectal cancer (mCRC) enrolled in the CORRECT trial. ASCO Meeting Abstracts 2015; 33 (Suppl. 15): 3558.
29. Rechsteiner M, Wild P, Kiessling MK et al. A novel germline mutation of PDGFR-b might be associated with clinical response of colorectal cancer to regorafenib. Ann Oncol 2015; 26 (1): 246–8с.
30. Guida T, Anaganti S, Provitera L et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res 2007; 13: 3363–9.
31. Loaiza-Bonilla A, Jensen CE, Shroff S et al. KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer. Cureus 2016; 8 (2): e478.
32. Kang HJ, Koh KH, Yang E et al. Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations. Proteomics 2006; 6: 11517.
33. Rajendra R, Pollack SM, Jones RL. Management of gastrointestinal stromal tumors. Future Oncol 2013; 9: 193206.
34. Blanke CD, Rankin C, Demetri GD et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008; 26 (4): 626–32.
35. Demetri GD, Reichardt P, Kang YK et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381 (9863): 295–302.
36. Maleddu A, Pantaleo MA, Nannini M et al. Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncol Rep 2009; 21: 1359–66.
37. Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev 2007; 17: 3–7.
38. Heinrich MC, Maki RG, Corless CL et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26: 5352–9.
39. Gounder MM, Maki RG. Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor. Cancer Chem Pharm 2011; 67 (Suppl. 1): S25–S43.
40. George S, von Mehren M, Heinrich MC et al. A multicenter phase II study of regorafenib in patients with advanced gastrointestinal stromal tumor after therapy with imatinib and sunitinib. J Clin Oncol 2011; 29: 10007.
41. Cheng AL, Kang YK, Lin DY et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067–75.
42. Cheng A-L, Finn RS, Qin S. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). J Clin Oncol 2017; 35 (15). Suppl.: 4001.
43. Bruix J, Merle P, Granito A et al. Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial (abstract LBA-03). Ann Oncol 2016; 27 (Suppl. 2): ii140–ii141.
44. Kudo M. Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016; 5: 235–44.
45. A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib. Liver Cancer 2017; 6 (3): 177–84.
46. Bruix J et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J Hepatol 2012; 57, Issue 4: 821–9.
Авторы
М.Ю.Федянин*, А.А.Трякин
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*fedianinmu@mail.ru
N.N.Blokhin National Medical Reseach Center of Oncology of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*fedianinmu@mail.ru
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*fedianinmu@mail.ru
________________________________________________
N.N.Blokhin National Medical Reseach Center of Oncology of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*fedianinmu@mail.ru
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