Regorafenib as a single-agent in the treatment of patients with gastrointestinal tumors: an overview for pharmacists

Targeted Oncology

Volumn 10, Issue 2, 2015, Pages 199-213

  Rey, Jean Baptiste ^a   Launay Vacher, Vincent ^b   Tournigand, Christophe ^c  

^a INSTITUT JEAN GODINOT   (France)

^b PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^c HENRI MONDOR HOSPITAL   (France)

Author keywords

Gastrointestinal tumors; Multi tyrosine kinase inhibitor; Pharmacist; Regorafenib

Indexed keywords

AFLIBERCEPT; ALANINE AMINOTRANSFERASE; ANGIOPOIETIN RECEPTOR; B RAF KINASE; BEVACIZUMAB; CD135 ANTIGEN; FIBROBLAST GROWTH FACTOR RECEPTOR 1; OXALIPLATIN; PLACEBO; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN RET; RAF PROTEIN; REGORAFENIB; SORAFENIB; TRIACYLGLYCEROL LIPASE; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; CARBANILAMIDE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE;

AEROBIC METABOLISM; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; CELL PROLIFERATION; CELL STIMULATION; COLORECTAL CANCER; DIARRHEA; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENZYME INHIBITION; FATIGUE; GASTROINTESTINAL TUMOR; GENE MUTATION; GLIOBLASTOMA; HAND FOOT SYNDROME; HEART ARREST; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HUMAN; HYPERBILIRUBINEMIA; HYPERTENSION; HYPERURICEMIA; HYPOPHOSPHATEMIA; IC50; LIVER CELL CARCINOMA; LIVER FAILURE; NONHUMAN; OVERALL SURVIVAL; PATIENT SATISFACTION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN PHOSPHORYLATION; QUALITY OF LIFE; RASH; RECOMMENDED DRUG DOSE; REVIEW; SIGNAL TRANSDUCTION; SKIN TOXICITY; THROMBOCYTOPENIA; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; TUMOR VASCULARIZATION; ANIMAL; DRUG EFFECTS; DRUG INTERACTION; ENZYMOLOGY; GASTROINTESTINAL NEOPLASMS; PATHOLOGY; PHARMACIST; TREATMENT OUTCOME;

ANIMALS; DRUG INTERACTIONS; GASTROINTESTINAL NEOPLASMS; HUMANS; PHARMACISTS; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS; PYRIDINES; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84930652419     PISSN: 17762596     EISSN: 1776260X     Source Type: Journal    
DOI: 10.1007/s11523-014-0333-x     Document Type: Review

References (54)

1. Hu QD, Zhang Q, Chen W, Bai XL, Liang TB (2013) Human development index is associated with mortality-to-incidence ratios of gastrointestinal cancers. World J Gastroenterol 19:5261–5270
2. Prenen H, Vecchione L, Van Cutsem E (2013) Role of targeted agents in metastatic colorectal cancer. Target Oncol 8:83–96
3. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Kohne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, Jordan K, Meshcheryakov A, Papamichail D, Pfeiffer P, Souglakos I, Turhal S, Cervantes A (2012) ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol 23:2479–2516
4. National Comprehensive Cancer Network Guidelines Colon Cancer Version 3.2013 http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
5. Glivec® summary of product characteristics http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000406/WC500022207.pdf
6. SUTENT® summary of product characteristics http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000687/WC500057737.pdf
7. Nexavar® summary of product characterstics http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000690/WC500027704.pdf
8. Gossage L, Eisen T (2010) Targeting multiple kinase pathways: a change in paradigm. Clin Cancer Res 16:1973–1978
9. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, Thierauch KH, Zopf D (2011) 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 129:245–255
10. Stivarga® summary of product characteristics http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002573/WC500149164.pdf
11. Stivarga® (regorafenib) label- accessdata FDA http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204369lbl.pdf
12. EMA summary of opinion initial authorization—Stivarga® (regorafenib) http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/002573/WC500144844.pdf
13. Sessions JK, Valgus J, Barbour SY, Iacovelli L (2010) Role of oncology clinical pharmacists in light of the oncology workforce study. J Oncol Pract 6:270–272
14. Al-Quteimat OM, Al-Badaineh MA (2013) Role of oncology clinical pharmacist: a case of life-saving interventions. Int J Basic Clin Pharmacol 2:655–658
15. The NHS cancer plan and the pharmacy contribution to cancer care (January 2001) http://www.bopawebsite.org/contentimages/publications/OncologyPharmacy.pdf
16. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109
17. Zopf D, Heinig R, Schutz G, Thierauch K-H, Hirth-Dietrich C, Hafner F-T, Christensen O, Lin T, Wilhelm S, Radtke M (2010) Regorafenib (BAY 73–4506): identification of clinically relevant metabolites and their preclinical pharmacology. 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, April 17–21 Abstract 1666
18. Serrano-Garcia C, Heinrich MC, Zhu M, Raut CP, Eilers G, Ravegnini G, Demetri GD, Bauer S, Fletcher JA, George S (2013) In vitro and in vivo activity of regorafenib (REGO) in drug-resistant gastrointestinal stromal tumors (GIST). J Clin Oncol 31(Suppl):Abstract 10510
19. Abou-Elkacem L, Arns S, Brix G, Gremse F, Zopf D, Kiessling F, Lederle W (2013) Regorafenib inhibits growth, angiogenesis, and metastasis in a highly aggressive, orthotopic colon cancer model. Mol Cancer Ther 12:1322–1331
20. Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, Unger C, Kratzschmar J, Heinig R, Boix O, Christensen O (2012) 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 18:2658–2667
21. Strumberg D, Scheulen ME, Schultheis B, Richly H, Frost A, Buchert M, Christensen O, Jeffers M, Heinig R, Boix O, Mross K (2012) Regorafenib (BAY 73–4506) in advanced colorectal cancer: a phase I study. Br J Cancer 106:1722–1727
22. George S, Wang Q, Heinrich MC, Corless CL, Zhu M, Butrynski JE, Morgan JA, Wagner AJ, Choy E, Tap WD, Yap JT, Van den Abbeele AD, Manola JB, Solomon SM, Fletcher JA, von Mehren M, Demetri GD (2012) Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol 30(19):2401–2407
23. George S, Feng Y, von Mehren M, Choy E, Corless CL, Hornick JL, Butrynski JE, Wagner AJ, Solomon S, Morgan JA, Heinrich MC, Demetri GD (2013) Prolonged survival and disease control in the academic phase II trial of regorafenib in GIST: Response based on genotype. J Clin Oncol 31 (Suppl):Abstract 10511
24. Bruix J, Tak WY, Gasbarrini A, Santoro A, Colombo M, Lim HY, Mazzaferro V, Wiest R, Reig M, Wagner A, Bolondi L (2013) Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase II safety study. Eur J Cancer 49(16):3412–3419
25. Shimizu T, Tolcher AW, Patnaik A, Papadopoulos K, Christensen O, Lin T, R. BJG (2010) Phase I dose-escalation study of continuously administered regorafenib (BAY 73–4506), an inhibitor of oncogenic and angiogenic kinases, in patients with advanced solid tumors. J Clin Oncol 28 (15S):abstr 3035
26. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D, Group CS (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303–312
27. Siena S, Grothey A, Sobrero A, Falcone A, Ychou M, Lenz HJ, Yoshino T, Cihon F, Pawar V, Van Cutsem E (2013) Effects of regorafenib therapy on health-related quality of life in patients with metastatic colorectal cancer in the phase III CORRECT study. Eur J Cancer 49 (Suppl):Abstract 2156
28. Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schoffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG, investigators Gs (2013) 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 381:295–302
29. Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293–4300
30. Study of regorafenib after sorafenib in patients with hepatocellular carcinoma (RESORCE). ClinicalTrials.gov Identifier: NCT01774344 http://clinicaltrials.gov/ct2/show/record/NCT01774344 Accessed November 2013
31. National Cancer Institute FDA approval bevacizumab http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab
32. Avastin® summary of product characteristics http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000582/WC500029271.pdf
33. Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99:11393–11398
34. Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, Ruff P, van Hazel GA, Moiseyenko V, Ferry D, McKendrick J, Polikoff J, Tellier A, Castan R, Allegra C (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499–3506
35. ZALTRAP® (ziv-aflibercept) label access data FDA http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125418s000lbl.pdf
36. Trnkova ZJ, Grothey A, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Cihon F, Wagner A, Reif S, Smeets J, Diefenbach K, Laurent D, Van Cutsem E (2013) Population pharmacokinetics analysis of regorafenib and its active metabolites from the phase III CORRECT study of metastatic colorectal cancer. Ann Oncol 24(Suppl 4):iv37
37. Schultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, Hacker UT, Kohne CH, Kornacker M, Boix O, Lettieri J, Krauss J, Fischer R, Hamann S, Strumberg D, Mross KB (2013) 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 24:1560–1567
38. Grothey A, Sobrero AF, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Argiles G, Yoshino T, Lenz H-J, Goldberg RM, Sargent DJ, Cihon F, Wagner A, Cupit L, Laurent D, Van Cutsem E (2013) Time profile of adverse events (AEs) from regorafenib (REG) treatment for metastatic colorectal cancer (mCRC) in the phase III CORRECT study. J Clin Oncol 31 (Supp):Abstract 3637.
39. Belum VR, Wu S, Lacouture ME (2013) Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Invest New Drugs 31:1078–1086
40. Eisen T, Joensuu H, Nathan PD, Harper PG, Wojtukiewicz MZ, Nicholson S, Bahl A, Tomczak P, Pyrhonen S, Fife K, Bono P, Boxall J, Wagner A, Jeffers M, Lin T, Quinn DI (2012) Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol 13(10):1055–1062
41. Kies MS, Blumenschein Jr. GR, Christensen O, Lin T, Tolcher AW (2010) Phase I study of regorafenib (BAY 73–4506), an inhibitor of oncogenic and angiogenic kinases, administered continuously in patients (pts) with advanced refractory non-small cell lung cancer (NSCLC). J Clin Oncol 28 (15 Suppl):abstr 7585
42. Van Cutsem E, Alberto A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Argilés G, Yoshino T, Lenz H-J, Goldberg RM, Sargent DJ, Cihon F, Wagner A, Laurent D, Cupit L, Grothey A (2013) Regorafenib (REG) in progressive metastatic colorectal cancer (mCRC): Analysis of age subgroups in the phase III CORRECT trial. J Clin Oncol 31 (Suppl):Abstract 3636
43. Faivre S, Raymond E, Boucher E, Douillard J, Lim HY, Kim JS, Zappa M, Lanzalone S, Lin X, Deprimo S, Harmon C, Ruiz-Garcia A, Lechuga MJ, Cheng AL (2009) Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study. Lancet Oncol 10:794–800
44. Asian subjects with metastatic colorectal cancer treated with regorafenib or placebo after failure of standard therapy (CONCUR) ClinicalTrials.gov Identifier: NCT01584830. http://clinicaltrials.gov/show/NCT01584830. Accessed November 2013
45. Regorafenib + FOLFIRI versus placebo + FOLFIRI as 2nd line Tx in metastatic colorectal cancer ClinicalTrials.gov Identifier: NCT01298570 http://clinicaltrials.gov/show/NCT01298570 Accessed November 2013
46. Douillard JY, Rong A, Sidhu R (2013) RAS mutations in colorectal cancer. N Engl J Med 369:2159–2160
47. Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, von Moos R, Vieitez JM, Bouche O, Borg C, Steffens CC, Alonso-Orduna V, Schlichting C, Reyes-Rivera I, Bendahmane B, Andre T, Kubicka S, Investigators MLS (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37
48. Regorafenib as adjuvant therapy for colorectal cancer (CRC) with resected liver metastases (COAST). ClinicalTrials.gov Identifier: NCT01939223. http://clinicaltrials.gov/show/NCT01939223 Accessed November 2013
49. Study to determine the efficacy of regorafenib in metastatic colorectal cancer patients and to discover biomarkers. ClinicalTrials.gov Identifier: NCT01949194. http://clinicaltrials.gov/show/NCT01949194 Accessed November 2013.
50. Regorafenib in frail and/or unfit for chemotherapy patients with metastatic colorectal cancer (REFRAME). ClinicalTrials.gov Identifier: NCT01875380. http://clinicaltrials.gov/show/NCT01875380 Accessed November 2013.
51. Argiles Martinez G, Troiani T, Rivera F, Sobrero A, Benson A, Guillen C, Garosi VL, Wagner A, Saunders M (2013) First-line treatment with regorafenib (REG) in combination with mFOLFOX6 (folinic acid + 5-fluorouracil [5-FU] + oxaliplatin) for metastatic colorectal cancer (mCRC): A single-arm, open-label phase II clinical trial. Eur J Cancer 49 (Supplement 2):Abstract 2367
52. First line treatment of metastatic colorectal cancer with mFOLFOX6 in combination with regorafenib. ClinicalTrials.gov Identifier: NCT01289821. http://clinicaltrials.gov/show/NCT01289821 Accessed November 2013
53. A randomised phase II double-blind study of regorafenib or placebo in refractory advanced oesophago-gastric cancer (AOGC). ACTRN.org Identifier: ACTRN12612000239864. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000239864 Accessed November 2013
54. FOLFOX plus regorafenib in patients with unresectable or metastatic esophagogastric cancer. ClinicalTrials.gov Identifier: NCT01913639. http://clinicaltrials.gov/show/NCT01913639 Accessed November 2013.