https://hemonc.org/w/api.php?action=feedcontributions&user=Cmmicheel&feedformat=atomHemOnc.org - A Hematology Oncology Wiki - User contributions [en]2024-03-28T11:53:54ZUser contributionsMediaWiki 1.35.14https://hemonc.org/w/index.php?title=Olaparib_(Lynparza)&diff=41924Olaparib (Lynparza)2020-01-09T00:16:56Z<p>Cmmicheel: /* gBRCAm Breast cancer */</p>
<hr />
<div>==General information==<br />
Class/mechanism: PARP (poly-ADP (adenosine diphosphate)–ribose polymerase) inhibitor. PARP participates in the alternative base-excision repair pathway that helps to repair single-strand DNA breaks. PARP is involved in normal cellular homeostasis processes during DNA transcription and cell cycle regulation. By inhibiting PARP1, PARP2, and PARP3, olaparib leads to the accumulation of single-strand breaks. In patients with a concurrent BRCA1/BRCA2 mutation, in which there are also defects in homologous recombination double strand DNA repair, this inhibition of PARP enzymatic activity and formation of the PARP-DNA complex can lead to irrecoverable DNA damage and cell death.<ref name=insert>[https://www.azpicentral.com/lynparza/lynparza.pdf Olaparib (Lynparza) package insert]</ref><ref>[[Media:Olaparib.pdf|Olaparib (Lynparza) package insert (locally hosted backup)]]</ref><ref>[http://lynparza.com/ Lynparza manufacturer's website]</ref><br />
<ref>Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. Epub 2009 Jun 24. [https://www.nejm.org/doi/full/10.1056/NEJMoa0900212 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19553641 PubMed]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Breast cancer]]<br />
*[[Ovarian cancer]]<br />
*[[Pancreatic cancer]]<br />
*[[Prostate cancer]]<br />
<br />
==Patient drug information==<br />
*[https://www.azpicentral.com/lynparza/lynparza.pdf Olaparib (Lynparza) package insert]<ref name="insert"></ref><br />
*[http://chemocare.com/chemotherapy/drug-info/Olaparib.aspx Olaparib (Lynparza) patient drug information (Chemocare)]<ref>[http://chemocare.com/chemotherapy/drug-info/Olaparib.aspx Olaparib (Lynparza) patient drug information (Chemocare)]</ref><br />
*[http://www.uptodate.com/contents/olaparib-patient-drug-information Olaparib (Lynparza) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/olaparib-patient-drug-information Olaparib (Lynparza)patient drug information (UpToDate)]</ref><br />
<br />
==History of changes in FDA indication==<br />
===[[Breast_cancer,_BRCA-mutated|gBRCAm Breast cancer]]===<br />
*1/12/2018: Granted regular FDA approval for the treatment of patients with deleterious or suspected deleterious [[Biomarkers#germline|germline]] [[Biomarkers#BRCA|BRCA]]-[[Biomarkers#mutation|mutated]] (gBRCAm), [[Biomarkers#ERBB2|HER2]]-[[Biomarkers#negative|negative]] [[Breast_cancer,_BRCA-mutated|metastatic breast cancer]] who have been treated with chemotherapy either in the neoadjuvant, adjuvant, or metastatic setting. Patients with [[Biomarkers#HR|hormone receptor (HR)]]-[[Biomarkers#positive|positive]] [[Breast_cancer|breast cancer]] should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine treatment. ''(New disease entity)''<br />
<br />
===[[Ovarian cancer]]===<br />
*12/19/2014: [https://wayback.archive-it.org/7993/20170111160837/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm Granted initial accelerated FDA approval] as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated (as detected by an FDA-approved test) advanced [[ovarian cancer]] who have been treated with three or more prior lines of chemotherapy.<br />
*8/17/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm572143.htm Granted regular FDA approval] for the maintenance treatment of adult patients with recurrent [[Ovarian cancer|epithelial ovarian, fallopian tube, or primary peritoneal cancer]], who are in a complete or partial response to [[:Category:Platinum agents|platinum-based]] chemotherapy. ''(Approval expanded to maintenance after second-line therapy)''<br />
*12/19/2018: Approved for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. ''(Approval expanded to maintenance after first-line therapy)''<br />
<br />
===[[Pancreatic cancer|gBRCAm Pancreatic cancer]]===<br />
*12/27/2019: Approved for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. ''(New disease entity)''<br />
<br />
==Also known as==<br />
*'''Code names:''' AZD2281, AZD-2281, KU-0059436<br />
*'''Brand name:''' Lynparza<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Protein expression-specific medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:PARP inhibitors]]<br />
<br />
[[Category:Breast cancer medications]]<br />
[[Category:Ovarian cancer medications]]<br />
[[Category:Pancreatic cancer medications]]<br />
[[Category:Prostate cancer medications]]<br />
<br />
[[Category:FDA approved in 2014]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Osimertinib_(Tagrisso)&diff=41906Osimertinib (Tagrisso)2020-01-09T00:10:39Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: Mutant-selective EGFR tyrosine kinase inhibitor. Osimertinib preferentially binds irreversibly to certain mutant forms of the epidermal growth factor receptor (EGFR) (T790M, L858R, and exon 19 deletion) at approximately 9-times lower concentrations than wild-type. Two pharmacologically-active metabolites of osimertinib, AZ7550 and AZ5104, also emerge at about 10% the level of osimertinib. AZ7550 had similar potency to osimertinib. AZ5104 had about 8-times greater potency against exon 19 deletion and T790M mutants than osimertinib and 15-times greater potency against wild-type EGFR. Osimertinib also inhibits activity of HER2, HER3, HER4, ACK1, and BLK.<ref name=insert>[http://www.azpicentral.com/tagrisso/tagrisso.pdf Osimertinib (Tagrisso) package insert]</ref><ref>[[Media:Osimertinib.pdf | Osimertinib (Tagrisso) package insert (locally hosted backup)]]</ref><ref>[https://www.tagrisso.com/ Tagrisso manufacturer's website]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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 prescribing information.<ref name="insert"></ref><br />
<br />
==Resistance mechanisms==<br />
*'''2019:''' Leonetti et al. [https://www.nature.com/articles/s41416-019-0573-8 Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer]<br />
<br />
==Diseases for which it is used==<br />
*[[Non-small_cell_lung_cancer,_EGFR-mutated|EGFR-mutated NSCLC]]<br />
<br />
==Patient drug information==<br />
*[http://www.azpicentral.com/tagrisso/tagrisso.pdf Osimertinib (Tagrisso) package insert]<ref name="insert"></ref><br />
*[http://chemocare.com/chemotherapy/drug-info/osimertinib.aspx Osimertinib (Tagrisso) patient drug information (Chemocare)]<ref>[http://chemocare.com/chemotherapy/drug-info/osimertinib.aspx Osimertinib (Tagrisso) patient drug information (Chemocare)]</ref><br />
*[http://www.uptodate.com/contents/osimertinib-patient-drug-information Osimertinib (Tagrisso) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/osimertinib-patient-drug-information Osimertinib (Tagrisso) patient drug information (UpToDate)]</ref><br />
<br />
==History of changes in FDA indication==<br />
*11/13/2015: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm472565.htm FDA granted accelerated approval] "for the treatment of patients with metastatic [[Biomarkers#EGFR|epidermal growth factor receptor (EGFR)]] T790M [[Biomarkers#mutation|mutation]]-positive [[Non-small_cell_lung_cancer|non-small cell lung cancer (NSCLC)]], as detected by an FDA-approved test, who have progressed on or after [[:Category:EGFR_inhibitors|EGFR tyrosine kinase inhibitor (TKI)]] therapy."<ref name="insert"></ref><br />
*3/30/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm549683.htm FDA granted regular approval] "for the treatment of patients with metastatic [[Biomarkers#EGFR|epidermal growth factor receptor (EGFR)]] T790M [[Biomarkers#mutation|mutation-positive]] [[Non-small_cell_lung_cancer|non-small cell lung cancer (NSCLC)]], as detected by an FDA-approved test, who have progressed on or after [[:Category:EGFR_inhibitors|EGFR tyrosine kinase inhibitor (TKI)]] therapy."<ref name="insert"></ref><br />
*4/18/2018: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm605113.htm FDA approved] "for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have [[Biomarkers#EGFR|epidermal growth factor receptor (EGFR)]] [[Biomarkers#exon|exon]] 19 [[Biomarkers#deletion|deletions]] or [[Biomarkers#exon|exon]] 21 L858R [[Biomarkers#mutation|mutations]], as detected by an FDA-approved test."<br />
<br />
==Also known as==<br />
*'''Code name:''' AZD9291<br />
*'''Brand name:''' Tagrisso<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Kinase inhibitors]]<br />
[[Category:EGFR inhibitors]]<br />
<br />
[[Category:Non-small cell lung cancer medications]]<br />
<br />
[[Category:FDA approved in 2015]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Panitumumab_(Vectibix)&diff=41896Panitumumab (Vectibix)2020-01-09T00:07:18Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: EGFR antagonist; recombinant human IgG2 kappa monoclonal antibody that binds to EGFR (human epidermal growth factor receptor), competitively inhibiting binding of epidermal growth factor (EGF). EGFR is overexpressed in certain cancers, such as colon & rectal cancer, and plays a role in the signal transduction pathways that lead to transcription of genes that promote cell growth, survival, and motility. Blocking EGFR in a population overexpressing EGFR has been observed to inhibit cell growth and induce apoptosis.<ref name="insert">[http://pi.amgen.com/united_states/vectibix/vectibix_pi.pdf Panitumumab (Vectibix) package insert]</ref><ref>[[Media:Panitumumab.pdf | Panitumumab (Vectibix) package insert (locally hosted backup)]]</ref><ref>[http://www.vectibix.com/ Vectibix manufacturer's website]</ref><br />
<br>Route: IV<br />
<br>Extravasation: no information<br />
<br />
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 prescribing information.<ref name="insert"></ref> <br />
<br />
==Diseases for which it is used==<br />
*[[Colon cancer]]<br />
*[[Head and neck cancer]]<br />
*[[Penile cancer]]<br />
<br />
==Patient drug information==<br />
*[http://chemocare.com/bio/panitumumab.asp Panitumumab (Vectibix) patient drug information (Chemocare)]<ref>[http://chemocare.com/bio/panitumumab.asp Panitumumab (Vectibix) patient drug information (Chemocare)]</ref><br />
*Brief patient counseling information can be found on page 15 of the [http://pi.amgen.com/united_states/vectibix/vectibix_pi.pdf#page=15 Panitumumab (Vectibix) package insert]<ref name="insert"></ref><br />
*[http://www.uptodate.com/contents/panitumumab-patient-drug-information Panitumumab (Vectibix) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/panitumumab-patient-drug-information Panitumumab (Vectibix) patient drug information (UpToDate)]</ref><br />
<br />
==History of changes in FDA indication==<br />
* 9/27/2006: Accelerated FDA approval "for the treatment of [[Biomarkers#EGFR|EGFR]]-[[Biomarkers#expression|expressing]], metastatic [[Colon cancer|colorectal carcinoma]] with disease progression on or following [[Fluorouracil (5-FU)|fluoropyrimidine-]], [[Oxaliplatin (Eloxatin)|oxaliplatin-]], and [[Irinotecan (Camptosar)|irinotecan-]] containing chemotherapy regimens."<br />
* 8/17/2012: Restriction placed: "'''not indicated''' for the treatment of patients with [[Biomarkers#KRAS|KRAS]] [[Biomarkers#mutation|mutation]]-positive mCRC or for whom [[Biomarkers#KRAS|KRAS]] mCRC status is unknown."<br />
* 5/23/2014: Label revised "for the treatment of [[Biomarkers#wild-type|wild-type]] [[Biomarkers#KRAS|KRAS]] ([[Biomarkers#exon|exon]] 2) metastatic [[Colon cancer|colorectal cancer (mCRC)]] as determined by an FDA-approved test for this use: <br />
# In combination with [[Colon_cancer#FOLFOX_.26_Panitumumab|FOLFOX]] for first-line treatment.<br />
# As monotherapy following disease progression after prior treatment with [[Fluorouracil (5-FU)|fluoropyrimidine]], [[Oxaliplatin (Eloxatin)|oxaliplatin]], and [[Irinotecan (Camptosar)|irinotecan-]] containing chemotherapy."<br />
<br />
==Also known as==<br />
*'''Generic names:''' ABX-EGF, clone E7.6.3<br />
*'''Brand name:''' Vectibix<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Intravenous medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Antibody medications]]<br />
[[Category:Anti-EGFR antibodies]]<br />
[[Category:EGFR inhibitors]]<br />
<br />
[[Category:Colon cancer medications]]<br />
[[Category:Head and neck cancer medications]]<br />
[[Category:Penile cancer medications]] <br />
<br />
[[Category:FDA approved in 2006]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Panitumumab_(Vectibix)&diff=41888Panitumumab (Vectibix)2020-01-09T00:03:30Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: EGFR antagonist; recombinant human IgG2 kappa monoclonal antibody that binds to EGFR (human epidermal growth factor receptor), competitively inhibiting binding of epidermal growth factor (EGF). EGFR is overexpressed in certain cancers, such as colon & rectal cancer, and plays a role in the signal transduction pathways that lead to transcription of genes that promote cell growth, survival, and motility. Blocking EGFR in a population overexpressing EGFR has been observed to inhibit cell growth and induce apoptosis.<ref name="insert">[http://pi.amgen.com/united_states/vectibix/vectibix_pi.pdf Panitumumab (Vectibix) package insert]</ref><ref>[[Media:Panitumumab.pdf | Panitumumab (Vectibix) package insert (locally hosted backup)]]</ref><ref>[http://www.vectibix.com/ Vectibix manufacturer's website]</ref><br />
<br>Route: IV<br />
<br>Extravasation: no information<br />
<br />
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 prescribing information.<ref name="insert"></ref> <br />
<br />
==Diseases for which it is used==<br />
*[[Colon cancer]]<br />
*[[Head and neck cancer]]<br />
*[[Penile cancer]]<br />
<br />
==Patient drug information==<br />
*[http://chemocare.com/bio/panitumumab.asp Panitumumab (Vectibix) patient drug information (Chemocare)]<ref>[http://chemocare.com/bio/panitumumab.asp Panitumumab (Vectibix) patient drug information (Chemocare)]</ref><br />
*Brief patient counseling information can be found on page 15 of the [http://pi.amgen.com/united_states/vectibix/vectibix_pi.pdf#page=15 Panitumumab (Vectibix) package insert]<ref name="insert"></ref><br />
*[http://www.uptodate.com/contents/panitumumab-patient-drug-information Panitumumab (Vectibix) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/panitumumab-patient-drug-information Panitumumab (Vectibix) patient drug information (UpToDate)]</ref><br />
<br />
==History of changes in FDA indication==<br />
* 9/27/2006: Accelerated FDA approval "for the treatment of [[Biomarkers#EGFR|EGFR]]-expressing, metastatic [[Colon cancer|colorectal carcinoma]] with disease progression on or following [[Fluorouracil (5-FU)|fluoropyrimidine-]], [[Oxaliplatin (Eloxatin)|oxaliplatin-]], and [[Irinotecan (Camptosar)|irinotecan-]] containing chemotherapy regimens."<br />
* 8/17/2012: Restriction placed: "'''not indicated''' for the treatment of patients with [[Biomarkers#KRAS|KRAS]] [[Biomarkers#mutation|mutation]]-positive mCRC or for whom [[Biomarkers#KRAS|KRAS]] mCRC status is unknown."<br />
* 5/23/2014: Label revised "for the treatment of [[Biomarkers#wild-type|wild-type]] [[Biomarkers#KRAS|KRAS]] ([[Biomarkers#exon|exon]] 2) metastatic [[Colon cancer|colorectal cancer (mCRC)]] as determined by an FDA-approved test for this use: <br />
# In combination with [[Colon_cancer#FOLFOX_.26_Panitumumab|FOLFOX]] for first-line treatment.<br />
# As monotherapy following disease progression after prior treatment with [[Fluorouracil (5-FU)|fluoropyrimidine]], [[Oxaliplatin (Eloxatin)|oxaliplatin]], and [[Irinotecan (Camptosar)|irinotecan-]] containing chemotherapy."<br />
<br />
==Also known as==<br />
*'''Generic names:''' ABX-EGF, clone E7.6.3<br />
*'''Brand name:''' Vectibix<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Intravenous medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Antibody medications]]<br />
[[Category:Anti-EGFR antibodies]]<br />
[[Category:EGFR inhibitors]]<br />
<br />
[[Category:Colon cancer medications]]<br />
[[Category:Head and neck cancer medications]]<br />
[[Category:Penile cancer medications]] <br />
<br />
[[Category:FDA approved in 2006]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Pembrolizumab_(Keytruda)&diff=41884Pembrolizumab (Keytruda)2020-01-09T00:00:05Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: PD-1 antibody. Pembrolizumab is a humanized monoclonal antibody which binds to the PD-1 receptor on T-cells. In some cancers, the PD-1 ligands are upregulated, which results in inhibition of T-cell immune surveillance of tumors. By blocking the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2, pembrolizumab decreases this immune system inhibition and facilitates anti-tumor immune response.<ref name="insert">[http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf Pembrolizumab (Keytruda) package insert]</ref><ref>[[Media:Pembrolizumab.pdf | Pembrolizumab (Keytruda) package insert (locally hosted backup)]]</ref><ref>[http://www.keytruda.com/hcp/ Keytruda manufacturer's website]</ref><br />
<br>Route: IV<br />
<br>Extravasation: no information<br />
<br />
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 prescribing information.<ref name=insert></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Bladder cancer]]<br />
*[[Cervical cancer]]<br />
*[[Colon cancer]]<br />
*[[Endometrial cancer]]<br />
*[[Gastric cancer]]<br />
*[[Head and neck cancer|Head and neck squamous cell carcinoma]]<br />
*[[Hepatocellular carcinoma]]<br />
*[[Hodgkin lymphoma]]<br />
*[[Melanoma]]<br />
*[[Merkel cell carcinoma]]<br />
*[[MSI-H or dMMR|MSI-H or dMMR tumors (tissue-agnostic)]]<br />
*[[Non-small cell lung cancer]]<br />
*[[Primary mediastinal B-cell lymphoma]]<br />
*[[Renal cell carcinoma]]<br />
*[[Small cell lung cancer]]<br />
<br />
==Patient drug information==<br />
*[http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf Pembrolizumab (Keytruda) package insert]<ref name="insert" /><br />
*[http://www.chemocare.com/chemotherapy/drug-info/Pembrolizumab.aspx Pembrolizumab (Keytruda) patient drug information (Chemocare)]<ref>[http://www.chemocare.com/chemotherapy/drug-info/Pembrolizumab.aspx Pembrolizumab (Keytruda) patient drug information (Chemocare)]</ref><br />
*[https://www.keytruda.com/static/pdf/patient-wallet-card.pdf Keytruda wallet card about side effects]<ref>[https://www.keytruda.com/static/pdf/patient-wallet-card.pdf Keytruda wallet card about side effects]</ref><br />
*[http://www.uptodate.com/contents/pembrolizumab-patient-drug-information Pembrolizumab (Keytruda) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/pembrolizumab-patient-drug-information Pembrolizumab (Keytruda) patient drug information (UpToDate)]</ref><br />
<br />
==[[Management checklist]]==<br />
*CBC, comprehensive metabolic panel, Mg, Phos, LDH, TSH. Consider baseline EKG and troponin.<br />
<br />
==History of changes in FDA indication==<br />
===[[Bladder cancer]]===<br />
*5/18/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm Regular approval] for patients with locally advanced or metastatic [[Bladder cancer|urothelial carcinoma]] who have disease progression during or following [[:Category:Platinum_agents|platinum-containing]] chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with [[:Category:Platinum_agents|platinum-containing]] chemotherapy. ''(New disease indication)''<br />
*5/18/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm Accelerated approval] for patients with locally advanced or metastatic [[Bladder cancer|urothelial carcinoma]] who are not eligible for [[Cisplatin (Platinol)|cisplatin-containing]] chemotherapy.<br />
*6/19/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-limits-use-tecentriq-and-keytruda-some-urothelial-cancer-patients Label revised] for the treatment of patients with locally advanced or metastatic [[bladder cancer|urothelial carcinoma]] who are not eligible for [[Cisplatin (Platinol)|cisplatin-containing]] therapy and whose tumors express [[Biomarkers#PD-L1|PD-L1]] (Combined Positive Score ≥ 10), or in patients who are not eligible for any [[:Category:Platinum_agents|platinum-containing]] chemotherapy regardless of [[Biomarkers#PD-L1|PD-L1]] status.<br />
<br />
===[[Cervical cancer]]===<br />
*6/12/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer-disease-progression-during-or-after-chemotherapy Approved] for patients with recurrent or metastatic [[cervical cancer]] with disease progression on or after chemotherapy whose tumors express [[Biomarkers#PD-L1|PD-L1]] (CPS ≥1) as determined by an FDA-approved test. ''(New disease indication)''<br />
<br />
===[[Endometrial cancer]]===<br />
*9/17/2019: Accelerated approval in combination with [[Lenvatinib (Lenvima)]] for the treatment of patients with advanced [[Endometrial cancer|endometrial carcinoma]] that is not [[Biomarkers#MSI-H|microsatellite instability high (MSI-H)]] or [[Biomarkers#dMMR|mismatch repair deficient (dMMR)]] and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. ''(New disease indication)''<br />
<br />
===[[Esophageal cancer]]===<br />
*7/30/2019: Approved for patients with recurrent, locally advanced or metastatic, [[Esophageal cancer|squamous cell carcinoma of the esophagus (ESCC)]] whose tumors express [[Biomarkers#PD-L1|PD-L1]] (Combined Positive Score [CPS] ≥10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. ''(New disease indication)''<br />
<br />
===[[Gastric cancer|Gastric or gastroesophageal junction adenocarcinoma]]===<br />
*9/22/2017: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-advanced-gastric-cancer Accelerated approval] for patients with recurrent locally advanced or metastatic, [[Gastric cancer|gastric or gastroesophageal junction adenocarcinoma]] whose tumors express [[Biomarkers#PD-L1|PD-L1]] as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy. ''(New disease indication)''<br />
<br />
===[[Hodgkin lymphoma|Classical Hodgkin lymphoma (cHL)]]===<br />
*3/14/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm558604.htm Accelerated approval] for the treatment of adult and pediatric patients with refractory [[Hodgkin lymphoma|classical Hodgkin lymphoma (cHL)]], or those who have relapsed after three or more prior lines of therapy. ''(New disease indication)''<br />
<br />
===[[Head and neck cancer|Head and neck squamous cell carcinoma]]===<br />
*8/5/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm515627.htm Label expanded] for the treatment of patients with recurrent or metastatic [[Head and neck cancer|head and neck squamous cell carcinoma (HNSCC)]] with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. ''(New disease indication)''<br />
*6/10/2019: Approved for the first-line treatment of patients with metastatic or unresectable recurrent [[Head and neck cancer|head and neck squamous cell carcinoma (HNSCC)]] in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose tumors express [[Biomarkers#PD-L1|PD‑L1]] (Combined Positive Score [CPS] ≥1) ''(Approval extended to first-line setting)''<br />
<br />
===[[Hepatocellular carcinoma]]===<br />
*11/9/2018: [https://www.fda.gov/drugs/fda-grants-accelerated-approval-pembrolizumab-hepatocellular-carcinoma Accelerated approval] for patients with [[Hepatocellular carcinoma|hepatocellular carcinoma (HCC)]] who have been previously treated with [[Sorafenib (Nexavar)|sorafenib]]. ''(New disease indication)''<br />
<br />
===[[Melanoma]]===<br />
*9/4/2014: Initial [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm412802.htm accelerated FDA approval] for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]] and disease progression following [[Ipilimumab (Yervoy)|ipilimumab]] and, if [[Biomarkers#BRAF|BRAF]] V600 [[Biomarkers#mutation|mutation]] positive, a [[:Category:BRAF_inhibitors|BRAF inhibitor]].<br />
*12/18/2015: Label expanded for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]]. ''(Requirement for progression removed)''<br />
*2/15/2019: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adjuvant-treatment-melanoma Approved] for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. ''(Indication expanded to adjuvant setting)''<br />
<br />
===[[Merkel cell carcinoma]]===<br />
*12/19/2018: [https://www.fda.gov/drugs/fda-approves-pembrolizumab-merkel-cell-carcinoma Approved] for adult and pediatric patients with recurrent locally advanced or metastatic [[Merkel cell carcinoma|Merkel cell carcinoma (MCC)]]. ''(New disease indication)''<br />
<br />
===[[MSI-H or dMMR|MSI-H or dMMR tumors (tissue-agnostic)]]===<br />
*5/23/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm Granted FDA accelerated approval] for adult and pediatric patients with unresectable or metastatic, [[Biomarkers#MSI-H|microsatellite instability-high (MSI-H)]] or [[Biomarkers#dMMR|mismatch repair deficient (dMMR)]] solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with [[Biomarkers#MSI-H|MSI-H]] or [[Biomarkers#dMMR|dMMR]] [[Colon cancer|colorectal cancer]] that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. ''(New disease-agnostic indication)''<br />
<br />
===[[Non-small cell lung cancer]]===<br />
*10/2/2015: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm465650.htm Accelerated approval] for the treatment of patients with metastatic [[Non-small_cell_lung_cancer|non-small cell lung cancer (NSCLC)]] whose tumors express [[Biomarkers#PD-L1|programmed death ligand 1 (PD-L1)]] as determined by an FDA-approved test, with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. Patients with [[Biomarkers#EGFR|EGFR]] or [[Biomarkers#ALK|ALK]] genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab. ''(New disease indication)''<br />
*10/24/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm526430.htm Label expanded] for the following indications:<br />
**Patients with metastatic [[Non-small_cell_lung_cancer|NSCLC]] whose tumors have high [[Biomarkers#PD-L1|PD-L1]] expression (Tumor Proportion Score [TPS] greater than or equal to 50%) as determined by an FDA-approved test, with no [[Biomarkers#EGFR|EGFR]] or [[Biomarkers#ALK|ALK]] genomic tumor [Biomarkers#alteration|aberrations]], and no prior systemic chemotherapy treatment for metastatic NSCLC. (''first-line indication with biomarker requirement'')<br />
**Patients with metastatic [[Non-small_cell_lung_cancer|NSCLC]] whose tumors express [[Biomarkers#PD-L1|PD-L1]] (TPS greater than or equal to 1%) as determined by an FDA-approved test, with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. Patients with [[Biomarkers#EGFR|EGFR]] or [[Biomarkers#ALK|ALK]] genomic tumor [[Biomarkers#alteration|aberrations]] should have disease progression on FDA-approved therapy for these [[Biomarkers#alteration|aberrations]] prior to receiving pembrolizumab.<br />
*5/10/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm558048.htm FDA accelerated approval] to be used in combination with [[Pemetrexed (Alimta)|pemetrexed]] and [[Carboplatin (Paraplatin)|carboplatin]] for the treatment of patients with previously untreated metastatic [[Non-small cell lung cancer|non-squamous non-small cell lung cancer (NSCLC)]]. (''first-line indication with histology requirement'')<br />
*8/20/2018: Granted regular approval in combination with [[Pemetrexed (Alimta)|pemetrexed]] and [[:Category:Platinum_agents|platinum]] as first-line treatment of patients with metastatic, [[Non-small cell lung cancer|non-squamous non-small cell lung cancer (NSqNSCLC)]], with no [[Biomarkers#EGFR|EGFR]] or [[Biomarkers#ALK|ALK]] genomic tumor [[Biomarkers#alteration|aberrations]]. (''conversion to regular approval'')<br />
* 10/30/2018: Approval expanded in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic [[Non-small cell lung cancer|squamous non-small cell lung cancer (NSCLC)]]. (''first-line indication with histology requirement'')<br />
* 4/11/2019: Approval expanded for the first-line treatment of patients with stage III [[Non-small_cell_lung_cancer|non-small cell lung cancer (NSCLC)]] who are not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC. Patients’ tumors must have no [[Biomarkers#EGFR|EGFR]] or [[Biomarkers#ALK|ALK]] genomic [[Biomarkers#alteration|aberrations]] and express [[Biomarkers#PD-L1|PD-L1]] (Tumor Proportion Score [TPS] greater than or equal to 1%) (''approval expanded to the non-metastatic setting'')<br />
<br />
===[[Primary mediastinal B-cell lymphoma]]===<br />
*6/13/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-treatment-relapsed-or-refractory-pmbcl FDA approval expanded] for the treatment of adult and pediatric patients with refractory [[Primary mediastinal B-cell lymphoma|primary mediastinal large B-cell lymphoma (PMBCL)]], or who have relapsed after two or more prior lines of therapy. ''(New disease indication)''<br />
<br />
===[[Renal cell carcinoma]]===<br />
*4/19/2019: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-plus-axitinib-advanced-renal-cell-carcinoma Approved] to be used together with axitinib for the first-line treatment of patients with advanced [[Renal cell carcinoma|renal cell carcinoma (RCC)]]. ''(New disease indication)''<br />
<br />
===[[Small cell lung cancer]]===<br />
*6/17/2019: Accelerated approval for patients with metastatic [[Small cell lung cancer|small cell lung cancer (SCLC)]] with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. ''(New disease indication)''<br />
<br />
==Also known as==<br />
*'''Code names:''' MK-3475, SCH 900475<br />
*'''Generic names:''' lambrolizumab<br />
*'''Brand name:''' Keytruda<br />
<br />
==References==<br />
<references /><br />
<br />
[[Category:Drugs]]<br />
[[Category:Intravenous medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Immunotherapeutic]]<br />
[[Category:T-cell activators]]<br />
[[Category:Antibody medications]]<br />
[[Category:Anti-PD-1 antibodies]]<br />
<br />
[[Category:Bladder cancer medications]]<br />
[[Category:Cervical cancer medications]]<br />
[[Category:Colon cancer medications]]<br />
[[Category:Endometrial cancer medications]]<br />
[[Category:Gastric cancer medications]]<br />
[[Category:Head and neck cancer medications]]<br />
[[Category:Hepatocellular carcinoma medications]]<br />
[[Category:Hodgkin lymphoma medications]]<br />
[[Category:Melanoma medications]] <br />
[[Category:Merkel cell carcinoma medications]]<br />
[[Category:MSI-H or dMMR medications]]<br />
[[Category:Non-small cell lung cancer medications]]<br />
[[Category:Primary mediastinal B-cell lymphoma medications]]<br />
[[Category:Renal cell carcinoma medications]]<br />
[[Category:Small cell lung cancer medications]]<br />
<br />
[[Category:FDA approved in 2014]]<br />
[[Category:EMA approved drugs]]<br />
[[Category:PMDA approved drugs]]<br />
[[Category:WHO Essential Cancer Medicine]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Ponatinib_(Iclusig)&diff=41841Ponatinib (Iclusig)2020-01-08T23:32:26Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: Tyrosine kinase inhibitor with multiple targets, including Bcr-Abl tyrosine kinase, the constitutively active tyrosine kinase resulting from the Philadelphia chromosome abnormality in CML, as well as VEGFR, PDGFR, FGFR, the SRC kinases, KIT, EPH receptors, RET, TIE2, and FLT3. Ponatinib is active against the Bcr-Abl T315I mutation.<ref name="insert">[http://iclusig.com/pi Ponatinib (Iclusig) package insert]</ref><ref>[[Media:Ponatinib.pdf | Ponatinib (Iclusig) package insert (locally hosted backup)]]</ref><ref>[http://iclusig.com/ Iclusig manufacturer's website]</ref><ref>[http://www.ariad.com/wt/tertiarypage/AP24534 Ariad's Ponatinib (AP24534) site]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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 prescribing information.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Chronic myelogenous leukemia]]<br />
*[[B-cell_acute_lymphoblastic_leukemia,_Ph-positive|Ph+ B-cell ALL]]<br />
<br />
==Patient drug information==<br />
*Patient counseling information can be found on [http://iclusig.com/pdf/FDA_Approved_PI.pdf#page=16 pages 16-17 of the Ponatinib (Iclusig) package insert]<ref name="insert"></ref><br />
<br />
==History of changes in FDA indication==<br />
*12/14/2012: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm332252.htm FDA approved] "for the treatment of adult patients with [[Chronic myelogenous leukemia|chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML)]] that is resistant or intolerant to prior [[:Category:Kinase inhibitors|tyrosine kinase inhibitor therapy]] or [[B-cell_acute_lymphoblastic_leukemia,_Ph-positive|Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL)]] that is resistant or intolerant to prior [[:Category:Kinase inhibitors|tyrosine kinase inhibitor therapy]]."<br />
*10/31/2013: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm373072.htm Suspended by FDA] because of the risk of life-threatening blood clots and severe narrowing of blood vessels.<br />
*12/20/2013: [http://www.iclusigrems.com/ REMS] program put in place and medication is once again available.<br />
*11/29/2016: FDA granted full approval "for the treatment of adult patients with chronic-phase, accelerated-phase, or blast-phase [[Chronic myelogenous leukemia | chronic myeloid leukemia (CML)]] or [[Biomarkers#BCR-ABL1|Philadelphia chromosome]]–positive [[B-cell_acute_lymphoblastic_leukemia,_Ph-positive | acute lymphoblastic leukemia (ALL)]] for whom no other tyrosine kinase inhibitor therapy is indicated; and for the treatment of adult patients with [[Biomarkers#BCR-ABL1|T315I]]–positive [[chronic myelogenous leukemia|CML]] (chronic phase, accelerated phase, or blast phase) or [[Biomarkers#BCR-ABL1|T315I]]-positive, [[Biomarkers#BCR-ABL1|Philadelphia chromosome]]–positive [[B-cell_acute_lymphoblastic_leukemia,_Ph-positive|ALL]]."<br />
<br />
==Also known as==<br />
*'''Code name:''' AP24534<br />
*'''Generic name:''' ponatinib hydrochloride<br />
*'''Brand name:''' Iclusig<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Kinase inhibitors]]<br />
[[Category:Bcr-Abl inhibitors]]<br />
[[Category:FGFR inhibitors]]<br />
[[Category:FLT3 inhibitors]]<br />
[[Category:KIT inhibitors]]<br />
[[Category:RET inhibitors]]<br />
[[Category:SRC inhibitors]]<br />
[[Category:VEGFR inhibitors]]<br />
[[Category:PDGFR inhibitors]]<br />
<br />
[[Category:B-cell acute lymphoblastic leukemia medications]]<br />
[[Category:Chronic myelogenous leukemia medications]]<br />
<br />
[[Category:REMS program]]<br />
[[Category:FDA approved in 2012]]<br />
[[Category:PMDA approved drugs]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Rucaparib_(Rubraca)&diff=41812Rucaparib (Rubraca)2020-01-08T23:18:44Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>=General information=<br />
Class/mechanism: PARP inhibitor. Rucaparib inhibits activity of the poly (ADP-ribose) polymerase (PARP) enzymes--including PARP-1, PARP-2, and PARP-3--and interferes with PARP-mediated DNA repair. PARP inhibitor cytotoxicity is believed to involve formation of PARP-DNA complexes, DNA damage, apotosis, and cell death. This cytotoxicity was observed to have increased cytotoxicity in cells with mutations in BRCA1, BRCA2, and other DNA repair genes.<ref name="insert">[https://clovisoncology.com/media/1094/rubraca-prescribing-info.pdf Rucaparib (Rubraca) package insert]</ref><ref>[[Media:Rucaparib.pdf | Rucaparib (Rubraca) package insert (locally hosted backup)]]</ref><ref>[http://rubraca.com/ Rubraca manufacturer's website]</ref><ref>[https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=594405 Rucaparib phosphate at NCI Drug Dictionary]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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 prescribing information.<ref name="insert" /><br />
<br />
==Diseases for which it is used==<br />
*[[Ovarian cancer]]<br />
<br />
==Patient drug information==<br />
*[https://clovisoncology.com/media/1094/rubraca-prescribing-info.pdf Rucaparib (Rubraca) package insert]<ref name="insert" /> <br />
<br />
==History of changes in FDA indication==<br />
*12/19/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm533891.htm FDA granted accelerated approval] "for treatment of patients with deleterious [[Biomarkers#BRCA|BRCA]] [[Biomarkers#Mutation|mutation]] ([[Biomarkers#germline|germline]] and/or [[Biomarkers#Somatic|somatic]]) associated advanced [[ovarian cancer]] who have been treated with two or more chemotherapies."<br />
*4/6/2018: FDA approved "for the maintenance treatment of recurrent [[Ovarian cancer|epithelial ovarian, fallopian tube, or primary peritoneal cancer]] who are in a complete or partial response to [[:Category:Platinum_agents|platinum-based]] chemotherapy."<br />
<br />
==Also known as==<br />
*'''Code names:''' CO-338, AG-014699, PF-0136738<br />
*'''Brand name:''' Rubraca<br />
<br />
==References==<br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:PARP inhibitors]]<br />
<br />
[[Category:Ovarian cancer medications]]<br />
[[Category:FDA approved in 2016]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Trametinib_(Mekinist)&diff=41805Trametinib (Mekinist)2020-01-08T23:14:07Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: Reversible [http://en.wikipedia.org/wiki/MAP2K1 MEK1 (mitogen-activated extracellular signal regulated kinase 1)] and [http://en.wikipedia.org/wiki/MAP2K2 MEK2] kinase inhibitor. MEK proteins are upstream and affect cellular proliferation by modulating the activity of the ERK (extracellular signal-related kinase) pathway. BRAF V600E mutations constitutively activate the BRAF pathway, which includes MEK1 and MEK2. By inhibiting MEK1 and MEK2, trametinib inhibits tumor cell growth that would otherwise be stimulated by constitutive activation from certain BRAF mutations.<ref name="insert">[http://www.pharma.us.novartis.com/product/pi/pdf/mekinist.pdf Trametinib (Mekinist) package insert]</ref><ref>[[Media:Trametinib.pdf|Trametinib (Mekinist) package insert (locally hosted backup)]]</ref><ref>[http://mekinist.com/ Mekinist manufacturer's website]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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 prescribing information.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Melanoma,_BRAF-mutated|BRAF-mutated melanoma]]<br />
*[[Non-small cell lung cancer, BRAF-mutated|BRAF-mutated NSCLC]]<br />
*[[Thyroid_cancer,_BRAF-mutated|BRAF-mutated anaplastic thyroid cancer]]<br />
*[[BRAF|BRAF-mutated tumors (disease-agnostic)]]<br />
<br />
==Patient drug information==<br />
*[http://www.pharma.us.novartis.com/product/pi/pdf/mekinist.pdf Trametinib (Mekinist) package insert]<ref name="insert"></ref><br />
<br />
==History of changes in FDA indication==<br />
*5/29/2013: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm354199.htm FDA approved] "for the treatment of patients with unresectable or metastatic [[melanoma]] with [[Biomarkers#BRAF|BRAF]] V600E or V600K [[Biomarkers#Mutation|mutations]] as detected by an FDA-approved test."<ref name="insert"></ref><br />
*1/10/2014: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm381159.htm FDA approved] in combination with [[Dabrafenib (Tafinlar)]] "for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]] with [[Biomarkers#BRAF|BRAF]] V600E or V600K [[Biomarkers#Mutation|mutations]] as detected by an FDA-approved test."<ref name="insert"></ref><br />
*6/22/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm564331.htm FDA approved] in combination with [[Dabrafenib (Tafinlar)]] "for patients with metastatic [[Non-small cell lung cancer|non-small cell lung cancer (NSCLC)]] with [[Biomarkers#BRAF|BRAF]] V600E [[Biomarkers#mutation|mutation]] as detected by an FDA-approved test."<br />
*4/30/2018: Regular FDA approval with [[Dabrafenib (Tafinlar)]] "in combination for the adjuvant treatment of patients with [[Melanoma|melanoma]] with [[Biomarkers#BRAF|BRAF]] V600E or V600K [[Biomarkers#mutation|mutations]], as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection."<br />
*5/4/2018: FDA approval with [[Dabrafenib (Tafinlar)]] "in combination for the treatment of patients with locally advanced or metastatic [[Thyroid cancer|anaplastic thyroid cancer (ATC)]] with [[Biomarkers#BRAF|BRAF]] V600E [[Biomarkers#mutation|mutation]] and with no satisfactory locoregional treatment options."<br />
<br />
==Also known as==<br />
*'''Code names:''' GSK-1120212, GSK1120212, JTP-74057<br />
*'''Generic name:''' trametinib dimethyl sulfoxide<br />
*'''Brand name:''' Mekinist<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Mutation-specific medications]]<br />
[[Category:Oral medications]]<br />
<br />
[[Category:Kinase inhibitors]]<br />
[[Category:MAP2K1 inhibitors]]<br />
[[Category:MAP2K2 inhibitors]]<br />
<br />
[[Category:BRAF medications]]<br />
[[Category:Melanoma medications]] <br />
[[Category:Non-small cell lung cancer medications]]<br />
[[Category:Thyroid cancer medications]]<br />
<br />
[[Category:FDA approved in 2013]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Vemurafenib_(Zelboraf)&diff=41785Vemurafenib (Zelboraf)2020-01-08T22:58:26Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: Tyrosine kinase inhibitor of some mutated forms of BRAF serine/threonine<br />
kinase, including BRAF V600E. Also has been observed to inhibit other tyrosine kinases such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR. Certain BRAF mutations, such as V600E, result in constitutive activation of cell proliferation pathways and tumor growth.<ref name="insert">[http://www.gene.com/gene/products/information/zelboraf/pdf/pi.pdf Vemurafenib (Zelboraf) package insert]</ref><ref>[[Media:Vemurafenib.pdf | Vemurafenib (Zelboraf) package insert (locally hosted backup)]]</ref><ref>[http://www.zelboraf.com Zelboraf manufacturer's website]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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 prescribing information.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Melanoma,_BRAF-mutated|BRAF-mutated melanoma]]<br />
*[[BRAF|BRAF-mutated tumors (tissue-agnostic)]]<br />
*[[Erdheim-Chester disease]]<br />
*[[Hairy cell leukemia]]<br />
*[[Langerhans cell histiocytosis]]<br />
*[[Multiple myeloma]]<br />
*[[Thyroid cancer]]<br />
<br />
==More drug information==<br />
*[http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=38eea320-7e0c-485a-bc30-98c3c45e2763 DailyMed information]<br />
*[http://www.uptodate.com/contents/vemurafenib-patient-drug-information Vemurafenib (Zelboraf) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/vemurafenib-patient-drug-information Vemurafenib (Zelboraf) patient drug information (UpToDate)]</ref><br />
<br />
==History of changes in FDA indication==<br />
*8/17/2011: Initial FDA approval "for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]] with [[BRAF]] V600E [[Biomarkers#mutation|mutation]] as detected by an FDA-approved test."<br />
** Limitation: vemurafenib "is '''not recommended''' for use in patients with [[Biomarkers#wilt-type|wild-type]] [[Biomarkers#BRAF|BRAF]] [[Melanoma|melanoma]]."<br />
*11/6/2017: Granted regular FDA approval "for the treatment of patients with [[Erdheim-Chester disease|Erdheim-Chester Disease (ECD)]] with [[Biomarkers#BRAF|BRAF]] V600 [[Biomarkers#Mutation|mutation]]."<br />
<br />
==Also known as==<br />
*'''Code names:''' PLX4032, RG7204, RO5185426<br />
*'''Brand name:''' Zelboraf<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Kinase inhibitors]]<br />
[[Category:BRAF inhibitors]]<br />
[[Category:MAP2K4 inhibitors]]<br />
[[Category:MAP3K20 inhibitors]]<br />
[[Category:MAP4K5 inhibitors]]<br />
<br />
[[Category:BRAF medications]]<br />
[[Category:Erdheim-Chester disease medications]]<br />
[[Category:Hairy cell leukemia medications]]<br />
[[Category:Langerhans cell histiocytosis medications]]<br />
[[Category:Melanoma medications]] <br />
[[Category:Multiple myeloma medications]]<br />
[[Category:Thyroid cancer medications]]<br />
<br />
[[Category:FDA approved in 2011]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Venetoclax_(Venclexta)&diff=41772Venetoclax (Venclexta)2020-01-08T22:46:54Z<p>Cmmicheel: /* Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) */</p>
<hr />
<div>==General information==<br />
Class/mechanism: From the [http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=698675 NCI Drug Dictionary]: An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. GDC-0199 mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.<ref name="insert">[http://www.rxabbvie.com/pdf/venclexta.pdf Venetoclax (Venclexta) package insert]</ref><ref>[[Media:Venetoclax.pdf| Venetoclax (Venclexta) package insert (locally hosted backup)]]</ref><ref>[https://www.venclexta.com/ Venclexta manufacturer's website]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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://reference.medscape.com/drug/zytiga-abiraterone-999651 Medscape], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Acute myeloid leukemia]]<br />
*[[Chronic lymphocytic leukemia|Chronic lymphocytic leukemia]]<br />
*[[Mantle cell lymphoma]]<br />
*[[Multiple myeloma]]<br />
<br />
==History of changes in FDA indication==<br />
===[[Acute myeloid leukemia]]===<br />
*11/21/2018: Approval expanded for use in combination with [[Azacitidine (Vidaza)|azacitidine]] or [[Decitabine (Dacogen)|decitabine]] or low-dose [[Cytarabine (Cytosar)|cytarabine]] for the treatment of newly-diagnosed [[Acute_myeloid_leukemia|acute myeloid leukemia (AML)]] in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. ''(New disease entity)''<br />
<br />
===[[Chronic lymphocytic leukemia|Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]]===<br />
*4/11/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm495351.htm Approved] for the treatment of patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL)]] with [[Biomarkers#17p|17p]] [[Biomarkers#deletion|deletion]], as detected by an FDA-approved test, who have received at least one prior therapy. ''(Initial approval)''<br />
*6/8/2018: Granted regular approval for patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]], with or without [[Biomarkers#17p|17p]] [[Biomarkers#deletion|deletion]], who have received at least one prior therapy. ''(Regular approval; Biomarker-specific indication relaxed)''<br />
*5/15/2019: Approved for adult patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]]. ''(Prior treatment exposure requirement removed)''<br />
<br />
==Also known as==<br />
*'''Code names:''' ABT-199, GDC-0199<br />
*'''Brand name:''' Venclexta<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Bcl-2 inhibitors]]<br />
<br />
[[Category:Acute myeloid leukemia medications]]<br />
[[Category:Chronic lymphocytic leukemia medications]]<br />
[[Category:Mantle cell lymphoma medications]]<br />
[[Category:Multiple myeloma medications]]<br />
<br />
[[Category:FDA approved in 2016]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Venetoclax_(Venclexta)&diff=41767Venetoclax (Venclexta)2020-01-08T22:42:05Z<p>Cmmicheel: /* Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) */</p>
<hr />
<div>==General information==<br />
Class/mechanism: From the [http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=698675 NCI Drug Dictionary]: An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. GDC-0199 mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.<ref name="insert">[http://www.rxabbvie.com/pdf/venclexta.pdf Venetoclax (Venclexta) package insert]</ref><ref>[[Media:Venetoclax.pdf| Venetoclax (Venclexta) package insert (locally hosted backup)]]</ref><ref>[https://www.venclexta.com/ Venclexta manufacturer's website]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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://reference.medscape.com/drug/zytiga-abiraterone-999651 Medscape], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Acute myeloid leukemia]]<br />
*[[Chronic lymphocytic leukemia|Chronic lymphocytic leukemia]]<br />
*[[Mantle cell lymphoma]]<br />
*[[Multiple myeloma]]<br />
<br />
==History of changes in FDA indication==<br />
===[[Acute myeloid leukemia]]===<br />
*11/21/2018: Approval expanded for use in combination with [[Azacitidine (Vidaza)|azacitidine]] or [[Decitabine (Dacogen)|decitabine]] or low-dose [[Cytarabine (Cytosar)|cytarabine]] for the treatment of newly-diagnosed [[Acute_myeloid_leukemia|acute myeloid leukemia (AML)]] in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. ''(New disease entity)''<br />
<br />
===[[Chronic lymphocytic leukemia|Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]]===<br />
*4/11/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm495351.htm Approved] for the treatment of patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL)]] with 17p [[Biomarkers#deletion|deletion]], as detected by an FDA-approved test, who have received at least one prior therapy. ''(Initial approval)''<br />
*6/8/2018: Granted regular approval for patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]], with or without 17p [[Biomarkers#deletion|deletion]], who have received at least one prior therapy. ''(Regular approval; Biomarker-specific indication relaxed)''<br />
*5/15/2019: Approved for adult patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]]. ''(Prior treatment exposure requirement removed)''<br />
<br />
==Also known as==<br />
*'''Code names:''' ABT-199, GDC-0199<br />
*'''Brand name:''' Venclexta<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Bcl-2 inhibitors]]<br />
<br />
[[Category:Acute myeloid leukemia medications]]<br />
[[Category:Chronic lymphocytic leukemia medications]]<br />
[[Category:Mantle cell lymphoma medications]]<br />
[[Category:Multiple myeloma medications]]<br />
<br />
[[Category:FDA approved in 2016]]</div>Cmmicheelhttps://hemonc.org/w/index.php?title=Venetoclax_(Venclexta)&diff=41765Venetoclax (Venclexta)2020-01-08T22:40:55Z<p>Cmmicheel: /* History of changes in FDA indication */</p>
<hr />
<div>==General information==<br />
Class/mechanism: From the [http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=698675 NCI Drug Dictionary]: An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. GDC-0199 mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.<ref name="insert">[http://www.rxabbvie.com/pdf/venclexta.pdf Venetoclax (Venclexta) package insert]</ref><ref>[[Media:Venetoclax.pdf| Venetoclax (Venclexta) package insert (locally hosted backup)]]</ref><ref>[https://www.venclexta.com/ Venclexta manufacturer's website]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
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://reference.medscape.com/drug/zytiga-abiraterone-999651 Medscape], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref><br />
<br />
==Diseases for which it is used==<br />
*[[Acute myeloid leukemia]]<br />
*[[Chronic lymphocytic leukemia|Chronic lymphocytic leukemia]]<br />
*[[Mantle cell lymphoma]]<br />
*[[Multiple myeloma]]<br />
<br />
==History of changes in FDA indication==<br />
===[[Acute myeloid leukemia]]===<br />
*11/21/2018: Approval expanded for use in combination with [[Azacitidine (Vidaza)|azacitidine]] or [[Decitabine (Dacogen)|decitabine]] or low-dose [[Cytarabine (Cytosar)|cytarabine]] for the treatment of newly-diagnosed [[Acute_myeloid_leukemia|acute myeloid leukemia (AML)]] in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. ''(New disease entity)''<br />
<br />
===[[Chronic lymphocytic leukemia|Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]]===<br />
*4/11/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm495351.htm Approved] for the treatment of patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL)]] with 17p [[Biomarkers#deletion|deletion]], as detected by an FDA-approved test, who have received at least one prior therapy. ''(Initial approval)''<br />
*6/8/2018: Granted regular approval for patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]], with or without 17p deletion, who have received at least one prior therapy. ''(Regular approval; Biomarker-specific indication relaxed)''<br />
*5/15/2019: Approved for adult patients with [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)]]. ''(Prior treatment exposure requirement removed)''<br />
<br />
==Also known as==<br />
*'''Code names:''' ABT-199, GDC-0199<br />
*'''Brand name:''' Venclexta<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
[[Category:Mutation-specific medications]]<br />
<br />
[[Category:Bcl-2 inhibitors]]<br />
<br />
[[Category:Acute myeloid leukemia medications]]<br />
[[Category:Chronic lymphocytic leukemia medications]]<br />
[[Category:Mantle cell lymphoma medications]]<br />
[[Category:Multiple myeloma medications]]<br />
<br />
[[Category:FDA approved in 2016]]</div>Cmmicheel