Difference between revisions of "Regorafenib (Stivarga)"

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(regorafenib FDA approval)
m (Text replacement - "[http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or" to "or")
 
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'''FDA approved 9/27/2012'''.  Also known as BAY 73-4506.
 
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==General information==
 
==General information==
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Class/mechanism: Small molecule inhibitor of multiple tyrosine kinases, such as: VEGFR1, VEGFR2, VEGFR3, KIT, RET, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl which are involved in tumor cell proliferation, survival, and angiogenesis.  Its major active metabolites are M-2 and M-5.<ref name="insert">[http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf Regorafenib (Stivarga) package insert]</ref><ref>[[Media:Regorafenib.pdf | Regorafenib (Stivarga) package insert (locally hosted backup)]]</ref><ref>[http://www.stivarga.com Stivarga manufacturer's website]</ref>
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Class/mechanism: Small molecule inhibitor of multiple tyrosine kinases, such as: VEGFR1, VEGFR2, VEGFR3, KIT, RET, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl, which are involved in tumor cell proliferation, survival, and angiogenesis.  Its major active metabolites are M-2 and M-5.<ref name="insert">[http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf Regorafenib (Stivarga) package insert]</ref><ref>[[:File:Regorafenib.pdf | Regorafenib (Stivarga) package insert (locally hosted backup)]]</ref><ref>[http://www.stivarga.com Stivarga manufacturer's website]</ref>
 
<br>Route: PO
 
<br>Route: PO
 
<br>Extravasation: n/a
 
<br>Extravasation: n/a
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<br>'''Black Box Warning: Severe and sometimes fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue regorafenib for hepatotoxicity as manifested by elevated liver function tests (LFTs) or hepatocellular necrosis, depending upon severity and persistence.'''
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, or the package insert.<ref name="insert"></ref>
  
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer.  Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the package insert.
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==Diseases for which it is established ''(work in progress)''==
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*[[Colorectal cancer]]
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*[[Gastrointestinal stromal tumor]]
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*[[Hepatocellular carcinoma]]
  
 
==Diseases for which it is used==
 
==Diseases for which it is used==
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*[[Colon cancer]]
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*[[Cholangiocarcinoma]]
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*[[Gallbladder cancer]]
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*[[Gastric cancer]]
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*[[Leiomyosarcoma]]
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*[[Osteosarcoma]]
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*[[Renal cell carcinoma]]
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*[[Soft tissue sarcoma]]
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==Patient drug information==
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*[http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf Regorafenib (Stivarga) package insert]<ref name="insert"></ref>
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*[https://chemocare.com/druginfo/regorafenib.aspx Regorafenib (Stivarga) patient drug information (Chemocare)]<ref>[https://chemocare.com/druginfo/regorafenib.aspx Regorafenib (Stivarga) patient drug information (Chemocare)]</ref>
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*[http://www.uptodate.com/contents/regorafenib-patient-drug-information Regorafenib (Stivarga) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/regorafenib-patient-drug-information Regorafenib (Stivarga) patient drug information (UpToDate)]</ref>
  
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==Clinical trials==
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==History of changes in FDA indication==
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*CORRECT: A randomized, double-blind, placebo-controlled phase III study of regorafenib plus BSC versus placebo plus BSC in patients with metastatic colorectal cancer (CRC) who have progressed after standard therapy [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=115&abstractID=87795 2012 ASCO Gastrointestinal Cancers Symposium abstract LBA385];<ref>Axel Grothey, Alberto F. Sobrero, Salvatore Siena, Alfredo Falcone, Marc Ychou, Heinz-Josef Lenz, Takayuki Yoshino, Frank Cihon, Andrea Wagner, Eric Van Cutsem, on behalf of the CORRECT Study Team. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. 2012 ASCO Gastrointestinal Cancers Symposium abstract LBA385 [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=115&abstractID=87795 link to abstract]</ref> [http://clinicaltrials.gov/show/NCT01103323 Clinicaltrials.gov NCT01103323]; [http://healthcare.bayer.com/scripts/pages/en/research_development/clinical_trials/trial_finder/trialfinder_detail.php?trialid=14387 Bayer study 14387]
 
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*Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor after  Failure with Imatinib or Sunitinib;<ref>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. 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. 2012 Jul 1;30(19):2401-7. Epub 2012 May 21. [http://jco.ascopubs.org/content/30/19/2401.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22614970 PubMed]</ref> [http://clinicaltrials.gov/ct2/show/NCT01068769 Clinicaltrials.gov NCT01068769]
 
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*[http://www.cancer.gov/clinicaltrials/search/results?protocolsearchid=6566374 List of regorafenib clinical trials at Cancer.gov]
 
  
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==Patient drug information==
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===[[Colorectal cancer]]===
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*[http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf#page=15 Regorafenib (Stivarga) package insert PDF pages 15-18]<ref name="insert"></ref>
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*2012-09-27: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm321378.htm Approved] for patients with metastatic [[colorectal cancer]] (mCRC) who have been previously treated with [[Regimen_classes#Fluoropyrimidine-based_regimen|fluoropyrimidine-]], [[Regimen_classes#Oxaliplatin-based_regimen|oxaliplatin-]], and [[Regimen_classes#Irinotecan-based_regimen|irinotecan-based]] chemotherapy, an [[Regimen_classes#VEGFR_inhibitor_therapy|anti-VEGF therapy]], and, if KRAS wild type, an [[Regimen_classes#EGFR_TKI_therapy|anti-EGFR therapy]]. ''(Based on CORRECT)''
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===[[Gastrointestinal stromal tumor]]===
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*2013-02-25: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340958.htm Approved] for patients with advanced [[Gastrointestinal stromal tumor|gastrointestinal stromal tumors (GIST)]] that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease. ''(Based on GRID)''
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===[[Hepatocellular carcinoma]]===
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*2017-04-27: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm555548.htm Approved] for the treatment of patients with [[Hepatocellular carcinoma|hepatocellular carcinoma (HCC)]] who have been previously treated with [[Sorafenib (Nexavar)|sorafenib]]. ''(Based on RESORCE)''
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==History of changes in EMA indication==
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*2013-08-26: Initial marketing authorization as Stivarga.
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==History of changes in Health Canada indication==
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*2013-03-11: Initial notice of compliance for the treatment of patients with metastatic [[Colorectal cancer|colorectal cancer (CRC)]] who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor (anti-VEGF) therapy, and, if KRAS wild type, an anti-epidermal growth factor receptor (anti-EGFR) therapy.
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*2013-10-14: New indication for adult patients with metastatic and/or unresectable [[Gastrointestinal stromal tumor|GIST]] who have had disease progression on or intolerance to imatinib mesylate and sunitinib malate treatment.
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*2017-08-29: Indication revised for the treatment of patients with metastatic [[Colorectal cancer|colorectal cancer (CRC)]] who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor (anti-VEGF) therapy, and, if RAS wild type, an anti-epidermal growth factor receptor (anti-EGFR) therapy.
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*2017-09-18: New indication for use in the treatment of patients with [[Hepatocellular carcinoma|hepatocellular carcinoma (HCC)]] who have been previously treated with one systemic therapy.
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==History of changes in PMDA indication==
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*2013-03-25: Initial approval for the treatment of unresectable advanced or recurrent [[colorectal cancer]].
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*2013-08-20: New additional indication for the treatment of [[gastrointestinal stromal tumor]] which has progressed after cancer chemotherapy.
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*2017-06-26: New additional indication for the treatment of unresectable [[hepatocellular carcinoma]] which has progressed after cancer chemotherapy.
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==Also known as==
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*'''Code name:''' BAY 73-4506
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*'''Brand names:''' Nublexa, Regonix, Renib, Resihance, Stivarga
  
 
==References==
 
==References==
 
<references/>
 
<references/>
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[[Category:Drugs]]
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[[Category:Oral medications]]
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[[Category:BRAF inhibitors]]
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[[Category:FGFR inhibitors]]
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[[Category:KIT inhibitors]]
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[[Category:PDGFR inhibitors]]
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[[Category:RET inhibitors]]
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[[Category:TEK inhibitors]]
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[[Category:VEGFR inhibitors]]
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[[Category:Cholangiocarcinoma medications]]
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[[Category:Colorectal cancer medications]]
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[[Category:Gallbladder cancer medications]]
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[[Category:Gastric cancer medications]]
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[[Category:Gastrointestinal stromal tumor medications]]
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[[Category:Hepatocellular carcinoma medications]]
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[[Category:Leiomyosarcoma medications]]
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[[Category:Osteosarcoma medications]]
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[[Category:Renal_cell_carcinoma medications]]
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[[Category:Soft tissue sarcoma medications]]
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[[Category:EMA approved in 2013]]
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[[Category:FDA approved in 2012]]
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[[Category:Health Canada approved in 2013]]
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[[Category:PMDA approved in 2013]]

Latest revision as of 00:15, 6 July 2024

General information

Class/mechanism: Small molecule inhibitor of multiple tyrosine kinases, such as: VEGFR1, VEGFR2, VEGFR3, KIT, RET, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl, which are involved in tumor cell proliferation, survival, and angiogenesis. Its major active metabolites are M-2 and M-5.[1][2][3]
Route: PO
Extravasation: n/a
Black Box Warning: Severe and sometimes fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue regorafenib for hepatotoxicity as manifested by elevated liver function tests (LFTs) or hepatocellular necrosis, depending upon severity and persistence.

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, or the package insert.[1]

Diseases for which it is established (work in progress)

Diseases for which it is used

Patient drug information

History of changes in FDA indication

Colorectal cancer

Gastrointestinal stromal tumor

Hepatocellular carcinoma

History of changes in EMA indication

  • 2013-08-26: Initial marketing authorization as Stivarga.

History of changes in Health Canada indication

  • 2013-03-11: Initial notice of compliance for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor (anti-VEGF) therapy, and, if KRAS wild type, an anti-epidermal growth factor receptor (anti-EGFR) therapy.
  • 2013-10-14: New indication for adult patients with metastatic and/or unresectable GIST who have had disease progression on or intolerance to imatinib mesylate and sunitinib malate treatment.
  • 2017-08-29: Indication revised for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor (anti-VEGF) therapy, and, if RAS wild type, an anti-epidermal growth factor receptor (anti-EGFR) therapy.
  • 2017-09-18: New indication for use in the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with one systemic therapy.

History of changes in PMDA indication

  • 2013-03-25: Initial approval for the treatment of unresectable advanced or recurrent colorectal cancer.
  • 2013-08-20: New additional indication for the treatment of gastrointestinal stromal tumor which has progressed after cancer chemotherapy.
  • 2017-06-26: New additional indication for the treatment of unresectable hepatocellular carcinoma which has progressed after cancer chemotherapy.

Also known as

  • Code name: BAY 73-4506
  • Brand names: Nublexa, Regonix, Renib, Resihance, Stivarga

References

  1. ↑ 1.0 1.1 1.2 Regorafenib (Stivarga) package insert
  2. ↑ Regorafenib (Stivarga) package insert (locally hosted backup)
  3. ↑ Stivarga manufacturer's website
  4. ↑ Regorafenib (Stivarga) patient drug information (Chemocare)
  5. ↑ Regorafenib (Stivarga) patient drug information (UpToDate)
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