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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All Drug Records" href="/books/n/livertox/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png" alt="Cover of LiverTox" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK597220_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK597220_dtls__"><div>Bethesda (MD): <a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>; 2012-.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/livertox/">Drug Records</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/livertox/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/livertox/Acyclovir/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/livertox/Adalimumab/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK597220_"><span class="title" itemprop="name">Adagrasib</span></h1><p class="small">Last Update: <span itemprop="dateModified">October 4, 2023</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Adagrasib.OVERVIEW"><h2 id="_Adagrasib_OVERVIEW_">OVERVIEW</h2><div id="Adagrasib.Introduction"><h3>Introduction</h3><p>Adagrasib is a small molecule inhibitor of the KRAS G12C mutant protein which is found in up to 13% of refractory cases of non-small cell lung cancer. Serum aminotransferase elevations are common during therapy with adagrasib, and a proportion of patients develop clinically apparent liver injury that can be severe.</p></div><div id="Adagrasib.Background"><h3>Background</h3><p>Adagrasib (a” dah gras’ ib) is an orally available, small molecule inhibitor of the KRAS gene product that is a frequently mutated oncogene found in several forms of cancer, most commonly in non-small cell lung cancer (NSCLC). The KRAS (Kristen rat sarcoma viral oncogene homolog) G12C mutation produces a constituently active protein receptor (a member of the RAS GTPase family) that stimulates excessive cell growth. Adagrasib binds to and locks the abnormal receptor into an inactive conformation, thereby inhibiting cell growth and proliferation in tumor cell lines and experimental tumor models with the KRAS G12C mutation. In large open label trials, adagrasib was found to induce objective responses in 43% of patients with refractory NSCLC harboring the KRAS G12C mutation. Adagrasib was granted accelerated approval in the United States in 2022 for adults with NSCLC with documented KRAS G12C mutations, the second small molecule inhibitor approved for this indication (the first being sotorasib). Adagrasib remains under evaluation for other forms of cancer harboring KRAS G12C mutations. Adagrasib is available in tablets of 200 mg under the brand name Krazati. The recommended dose is 600 mg orally twice daily until disease progression or unacceptable toxicity. Side effects of adagrasib are common and arise in almost all treated patients, leading to dose interruptions in 77%, dose modifications in 28%, and permanent discontinuation in 13% of treated patients. Common side effects include diarrhea, nausea and vomiting, decreased appetite, abdominal pain, fatigue, musculoskeletal pain, cough, dyspnea, edema, leukopenia, anemia, renal impairment, hypokalemia, hyponatremia, and aminotransferase elevations. Uncommon but potentially severe adverse events include gastrointestinal bleeding and obstruction, severe diarrhea or nausea, QTc interval prolongation, hepatotoxicity, and interstitial lung disease.</p></div><div id="Adagrasib.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>In the prelicensure clinical trials of adagrasib in patients with solid tumors harboring KRAS G12C mutations, liver test abnormalities were frequent although usually self-limited and mild. Some degree of <a class="def" href="/books/n/livertox/glossary/def-item/glossary.alanine-aminotransferase-alt-/">ALT</a> elevations arose in 28% to 46% of adagrasib treated patients and elevations above 5 times the upper limit of normal (ULN) were seen in 5% to 7%. In these trials that enrolled approximately 366 patients, adagrasib was discontinued early due to increased <a class="def" href="/books/n/livertox/glossary/def-item/glossary.aspartate-aminotransferase-ast-/">AST</a> or ALT in 8% of patients. In addition, a small proportion of patients developed clinically apparent hepatotoxicity requiring adagrasib discontinuation. The liver test abnormalities had a median onset of 3 weeks after initiation of therapy. While serum aminotransferase elevations were occasionally quite high (5 to 20 times ULN), there were no accompanying elevations in serum bilirubin and no patient developed clinically apparent liver injury with jaundice. The product label for adagrasib recommends monitoring for routine liver tests before, at 3 week intervals during the first 3 months of therapy, and thereafter as clinically indicated.</p><p><a class="def" href="/books/n/livertox/glossary/def-item/glossary.likelihood-score/">Likelihood score</a>: D (possible but infrequent cause of clinically apparent liver injury).</p></div><div id="Adagrasib.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The cause of serum aminotransferase elevations from adagrasib is unknown, but the pattern of abnormalities suggests immune-mediated liver injury. Several retrospective analyses have found that significant <a class="def" href="/books/n/livertox/glossary/def-item/glossary.alanine-aminotransferase-alt-/">ALT</a> and <a class="def" href="/books/n/livertox/glossary/def-item/glossary.aspartate-aminotransferase-ast-/">AST</a> elevations arise most frequently in patients receiving small molecule inhibitors who had received checkpoint inhibitor therapy (usually anti-PD-L1) within 3 months of starting. Furthermore, the histologic and clinical features of liver injury from tyrosine kinase and other small molecule inhibitors frequently resemble those of checkpoint inhibitors and a limited course of corticosteroids is often found to be beneficial.</p><p>Adagrasib is metabolized in the liver via the cytochrome P450 system, largely CYP 3A4, and is susceptible to drug-drug interactions with agents. Because of its known toxicity, drugs that inhibit or induce CYP 3A4 activity should be avoided or the dose of adagrasib should be adjusted according. Furthermore, drugs that are substrates of CYP 3A4 may be affected by concurrent treatment with adagrasib and should be avoided.</p></div><div id="Adagrasib.Outcome_and_Management"><h3>Outcome and Management</h3><p>The product label for adagrasib recommends monitoring for routine liver tests (<a class="def" href="/books/n/livertox/glossary/def-item/glossary.alanine-aminotransferase-alt-/">ALT</a>, <a class="def" href="/books/n/livertox/glossary/def-item/glossary.aspartate-aminotransferase-ast-/">AST</a>, alkaline phosphatase, and bilirubin) before starting treatment, monthly for the first 3 months of treatment and as clinically indicated thereafter. The dose of adagrasib should be reduced, held, or permanently discontinued based upon the severity of liver test abnormalities as described in the product label. In patients with jaundice or symptoms of liver injury accompanying the serum aminotransferase elevations, adagrasib should be promptly discontinued and not restarted. Cross sensitivity to liver injury is uncommon among the antineoplastic, small molecule enzyme and receptor inhibitors, but there is no information on shared adverse event sensitivity of adagrasib with other similar small molecule inhibitors such as sotorasib.</p><p>Drug Class: <a href="/books/n/livertox/AntineoplasticAgents/">Antineoplastic Agents</a>, <a href="/books/n/livertox/ProteinKinaseInhibit/">Protein Kinase Inhibitors</a></p><p>Other Related Drugs: <a href="/books/n/livertox/Sotorasib/">Sotorasib</a></p></div></div><div id="Adagrasib.PRODUCT_INFORMATION"><h2 id="_Adagrasib_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
|
||
</p><p>Adagrasib – Krazati®</p><p>
|
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<b>DRUG CLASS</b>
|
||
</p><p>Antineoplastic Agents</p><p>
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||
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Adagrasib" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
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</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div><div id="Adagrasib.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Adagrasib_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Adagrasib.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597220/table/Adagrasib.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Adagrasib.Tc_lrgtbl__"><table><thead><tr><th id="hd_h_Adagrasib.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_h_Adagrasib.Tc_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CAS REGISTRY NO.</th><th id="hd_h_Adagrasib.Tc_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Adagrasib.Tc_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Adagrasib.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adagrasib</td><td headers="hd_h_Adagrasib.Tc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/405243592" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2326521-71-3</a>
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</td><td headers="hd_h_Adagrasib.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C32-H35-Cl-F-N7-O2</td><td headers="hd_h_Adagrasib.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/405243592" title="View this structure in PubChem" class="img_link" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem"><img src="https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&sid=405243592" alt="image 405243592 in the ncbi pubchem database" /></a>
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</td></tr></tbody></table></div></div></div><div id="Adagrasib.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Adagrasib_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 04 October 2023</p><p>Abbreviations: KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer.</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Adagrasib.REF.zimmerman.1999">Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.<div><i>(Review of hepatotoxicity published in 1999 before the availability of small molecule enzyme and receptor inhibitors).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.deleve.2013">DeLeve LD. Kinase inhibitors. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 556.<div><i>(Review of hepatotoxicity of cancer chemotherapeutic agents, does not discuss adagrasib).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.wellstein.2018">Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.fda">FDA. <a href="https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216340Orig1s000MultidisciplineR.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>.accessdata<wbr style="display:inline-block"></wbr>.fda.gov/drugsatfda_docs<wbr style="display:inline-block"></wbr>/nda/2023/216340Orig1s000MultidisciplineR.pdf</a><div><i>(FDA website with initial multidiscipline clinical review of the safety and efficacy of adagrasib; states that the overall objective response rate was 43% in adults with NCSLC with KRAS p.G12C mutations and in a pooled safety review [n=366] most patients had at least one adverse event and 48% had a serious adverse event, 32% of patients had an ALT elevation, 5% were above 5 times ULN, and 1 patient [0.3%] developed anicteric drug induced liver injury, with signs of hypersensitivity that resolved on stopping therapy; there were cases of acute liver injury with jaundice or liver failure attributed with adagrasib).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.awad.2021.2382">Awad
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MM, Liu
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||
S, Rybkin
|
||
II, Arbour
|
||
KC, Dilly
|
||
J, Zhu
|
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VW, Johnson
|
||
ML, et al.
|
||
Acquired resistance to KRASG12C inhibition in cancer.
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||
N Engl J Med.
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||
2021;384:2382-2393. [<a href="/pmc/articles/PMC8864540/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8864540</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34161704" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34161704</span></a>]<div><i>(Among 38 patients being treated with adagrasib for advanced solid tumors harboring a KRAS G12C mutation who had an initial response to therapy but subsequent relapse or progression [“acquired resistance”], further mutations in KRAS DNA were found in DNA from tumor tissue and from circulating tumor DNA, mostly secondary mutations or amplifications in KRAS, but also in other genes in the signaling pathways or with histologic transformations).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.j_nne.2022.120">Jänne
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PA, Riely
|
||
GJ, Gadgeel
|
||
SM, Heist
|
||
RS, Ou
|
||
SI, Pacheco
|
||
JM, Johnson
|
||
ML, et al.
|
||
Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation.
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||
N Engl J Med.
|
||
2022;387:120-131. [<a href="https://pubmed.ncbi.nlm.nih.gov/35658005" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35658005</span></a>]<div><i>(Among 116 adult with NSCLC harboring a KRAS G12C mutation treated with adagrasib [600 mg twice daily for a median of 13 months], 43% had an objective response, while adverse events occurred in all treated subjects leading to dose interruption or modification in 83% and permanent discontinuation in 16%, and with ALT elevations in 28% which were above 5 times ULN in 5%).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.ou.2022.2530">Ou
|
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SI, Jänne
|
||
PA, Leal
|
||
TA, Rybkin
|
||
II, Sabari
|
||
JK, Barve
|
||
MA, Bazhenova
|
||
L, et al.
|
||
First-in-human phase I/IB dose-finding study of adagrasib (MRTX849) in patients with advanced KRAS/ G12C solid tumors (KRYSTAL-1).
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||
J Clin Oncol.
|
||
2022;40:2530-2538. [<a href="/pmc/articles/PMC9362872/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9362872</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35167329" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35167329</span></a>]<div><i>(Among 25 patients with advanced KRAS G12C mutant solid tumors treated with adagrasib [600 mg twice daily], the objective response rate was 53% in NSCLC, while the adverse event rate was 92% with nausea in 76%, diarrhea 70%, vomiting 48%, fatigue 40% and ALT elevations in 20% which were above 5 times ULN in 5%).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.dhillon.2023.275">Dhillon
|
||
S.
|
||
Adagrasib: first approval.
|
||
Drugs.
|
||
2023;83:275-285. [<a href="https://pubmed.ncbi.nlm.nih.gov/36763320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36763320</span></a>]<div><i>(Review of the mechanism of action, history of development, pharmacodynamics, clinical efficacy, and safety of adagrasib shortly after its initial approval in the US mentions that it has “manageable tolerability” with an overall adverse event rate of 97% with any liver test abnormality in 37% [among 366 treated patients] and ALT elevations in 28%, which were above 5 times the ULN in 4.3% and had a median time to onset of 3 weeks).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.adagrasib_krazati_for_nsclc.2023.e17">Adagrasib (Krazati) for NSCLC. Med Lett Drugs Ther.
|
||
2023;65:e17-e18. [<a href="https://pubmed.ncbi.nlm.nih.gov/36651795" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36651795</span></a>]<div><i>(Concise review of the mechanism of action, clinical efficacy, safety and costs of adagrasib, mentions that its effects were modest and that hepatotoxicity arose in more than 25% of patients, and that patients should be monitored for liver enzyme and bilirubin levels before and monthly for 3 months during therapy).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.chour.2023.1408">Chour
|
||
A, Denis
|
||
J, Mascaux
|
||
C, Zysman
|
||
M, Bigay-Game
|
||
L, Swalduz
|
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A, Gounant
|
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V, et al.
|
||
Brief report: severe sotorasib-related hepatotoxicity and non-liver adverse events associated with sequential anti-programmed cell death (ligand)1 and sotorasib therapy in KRASG12C-mutant lung cancer.
|
||
J Thorac Oncol.
|
||
2023;18(10):1408-1415. [<a href="https://pubmed.ncbi.nlm.nih.gov/37217096" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37217096</span></a>]<div><i>(Among 102 adults with refractory advanced NSCLC and KRAS G12C mutations treated with sotorasib in France outside of clinical trials, 48 who had received check point inhibitor therapy with anti-PD-L1 immediately before sotorasib had higher rates of severe adverse events [50% vs 13%] and higher rates of ALT elevations above 5 times ULN [33% vs 11%], although no fatal instances of hepatotoxicity occurred).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.desai.2023.100743">Desai
|
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A, Rakshit
|
||
S, Bansal
|
||
R, Ashara
|
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Y, Potter
|
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A, Manochakian
|
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R, Lou
|
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Y, et al.
|
||
Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report.
|
||
Cancer Treat Res Commun.
|
||
2023;36:100743. [<a href="https://pubmed.ncbi.nlm.nih.gov/37531736" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37531736</span></a>]<div><i>(Among 31 patients with advanced, refractory KRAS G12C-mutated NSCLC treated with sotorasib, 10 [32%] developed ALT elevations above 5 times ULN during therapy, all 10 had received previous check point inhibitor therapy [usually anti-PD-L1] and rates of ALT elevations were higher in those receiving checkpoint inhibitors within 30 days [3 of 4: 75%], than 30-90 days [7 of 11:65%], or greater than 90 days [none of 13: 0%], suggesting that sotorasib triggers a delayed immune mediated hepatotoxicity from anti-PD-L1 therapy if given within 3 months of stopping).</i></div></div></li><li><div class="bk_ref" id="Adagrasib.REF.zhang.2023.287">Zhang
|
||
J, Johnson
|
||
M, Barve
|
||
M, Bazhenova
|
||
L, McCarthy
|
||
M, Schwartz
|
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R, Horvath-Walsh
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E, Vet al. Practical guidance for the management of adverse events in patients with KRASG12C-mutated non-small cell lung cancer receiving adagrasib.
|
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Oncologist.
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||
2023;28:287-296. [<a href="/pmc/articles/PMC10078892/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10078892</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36892150" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36892150</span></a>]<div><i>(Review of the adverse events identified in trials of adagrasib and recommendations regarding monitoring and management based upon FDA labeling, mentions that liver enzymes [ALT, AST, Alk P] should be monitored every month for 3 months and that corticosteroid treatment can be considered for “significant hepatotoxicity”).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adagrasib. 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<a href="https://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&pubmedfilters=true&term=(Adagrasib/AE)+AND+Human%5BMH%5D+AND+(drug+induced+liver+injury+OR+jaundice/CI+OR+bile+duct+diseases/CI+OR+liver/DE+OR+liver+diseases/CI)+AND+(%221900/1/1%22%5BEDat%5D:%222999/12/31%22%5BEDat%5D)" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Recent References on Adagrasib: from PubMed.gov</a>
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Epub 2023 May 3.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/35167329" ref="ordinalpos=1&linkpos=2&log$=relatedarticles&logdbfrom=pubmed">First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRAS(G12C) Solid Tumors (KRYSTAL-1).</a><span class="source">[J Clin Oncol. 2022]</span><div class="brieflinkpop offscreen_noflow">First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRAS(G12C) Solid Tumors (KRYSTAL-1).<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Ou SI, Jänne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, Bazhenova L, Johnson ML, Velastegui KL, Cilliers C, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Clin Oncol. 2022 Aug 10; 40(23):2530-2538. Epub 2022 Feb 15.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/37327468" ref="ordinalpos=1&linkpos=3&log$=relatedarticles&logdbfrom=pubmed">Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRAS(G12C)-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases.</a><span class="source">[J Clin Oncol. 2023]</span><div class="brieflinkpop offscreen_noflow">Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRAS(G12C)-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Negrao MV, Spira AI, Heist RS, Jänne PA, Pacheco JM, Weiss J, Gadgeel SM, Velastegui K, Yang W, Der-Torossian H, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Clin Oncol. 2023 Oct 1; 41(28):4472-4477. Epub 2023 Jun 16.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/37782744" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Sotorasib.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Sotorasib.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/36763320" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Adagrasib: First Approval.</a><span class="source">[Drugs. 2023]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Adagrasib: First Approval.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Dhillon S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Drugs. 2023 Feb; 83(3):275-285. </em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=37956237" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=37956237" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67c8ddaba68b6b5afc6611ba">Adagrasib - LiverTox</a><div class="ralinkpop offscreen_noflow">Adagrasib - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67c8ddaaab82281a802dc5c8">Acyclovir - LiverTox</a><div class="ralinkpop offscreen_noflow">Acyclovir - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67c8ddaaa68b6b5afc660853">Acrivastine - LiverTox</a><div class="ralinkpop offscreen_noflow">Acrivastine - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67c8dda9b15b832ebc010166">Aclidinium - LiverTox</a><div class="ralinkpop offscreen_noflow">Aclidinium - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67c8dda8b15b832ebc00f8f7">Acitretin - LiverTox</a><div class="ralinkpop offscreen_noflow">Acitretin - LiverTox<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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