{"title":"The Pharmacologic Inhibition of KRAS Mutants as a Treatment for Cancer: Therapeutic Principles and Clinical Results.","authors":"Stefan Kasper, Martin Sebastian","doi":"10.3238/arztebl.m2025.0002","DOIUrl":"10.3238/arztebl.m2025.0002","url":null,"abstract":"<p><strong>Background: </strong>Mutations of the KRAS oncogene are found in up to 20% of all cancers, and particularly in non-small-cell lung cancer (NSCLC) (20-40%) and colorectal cancer (CRC) (30-50%). Inhibitors of specific KRAS mutants have recently become available and are now a part of routine care.</p><p><strong>Methods: </strong>This review is based on articles published in the past 5 years that were retrieved by a selective search in PubMed for clinical trials of the pharmacological inhibition of KRAS.</p><p><strong>Results: </strong>Sotorasib and adagrasib have already been approved, on the basis of two randomized phase III trials, as specific inhibitors of the KRASG12C mutant for palliative second-line treatment. Compared to standard chemotherapy with docetaxel, both drugs significantly prolonged progression-free survival (PFS): 5.6 months (95% confidence interval [4.3; 7.8]) for sotorasib versus 4.5 [3.0; 5.7] for docetaxel, and 5.5 months [4.5; 6.7] for adagrasib versus 3.8 [2.7; 4.7] for docetaxel. Sotorasib was also found to cause fewer severe adverse drug events (33%, versus 40% with docetaxel). The most common ones were diarrhea and elevated liver enzymes. For already treated CRC, sotorasib combined with the anti-epidermal growth factor receptor (anti-EGFR) antibody panitumumab was found, in a randomized phase III trial, to prolong progression-free survival significantly compared to standard therapy with triflurdin/tipiracil or regorafenib (5.6 months [4.2; 6.3] versus 2.2 months [1.9; 3.9]), while also improving patients' quality of life. Approval by the European Medicines Agency is pending. Further KRAS and pan-RAS inhibitors are now in early clinical development.</p><p><strong>Conclusion: </strong>Pharmacological KRAS inhibition is a promising new approach to the treatment of many kinds of cancer.</p>","PeriodicalId":11258,"journal":{"name":"Deutsches Arzteblatt international","volume":" Forthcoming","pages":"163-167"},"PeriodicalIF":6.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diabetic Coma Is Missing.","authors":"Ernst-Adolf Chantelau","doi":"10.3238/arztebl.m2024.0205","DOIUrl":"https://doi.org/10.3238/arztebl.m2024.0205","url":null,"abstract":"","PeriodicalId":11258,"journal":{"name":"Deutsches Arzteblatt international","volume":"122 6","pages":"m1019"},"PeriodicalIF":6.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evelyn Kusi, Muhammad Helmi Barghouth, Mascha Kern, Alex Müller, Norma Bethke, Stefanie Theuring, Joachim Seybold
{"title":"Genital Mutilation/Cutting in Female Asylum-Seekers—Findings of a Survey in Berlin, 2018–2022.","authors":"Evelyn Kusi, Muhammad Helmi Barghouth, Mascha Kern, Alex Müller, Norma Bethke, Stefanie Theuring, Joachim Seybold","doi":"10.3238/arztebl.m2024.0241","DOIUrl":"https://doi.org/10.3238/arztebl.m2024.0241","url":null,"abstract":"","PeriodicalId":11258,"journal":{"name":"Deutsches Arzteblatt international","volume":"122 6","pages":"168-169"},"PeriodicalIF":6.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Accessibility of Stroke Units in Germany.","authors":"Niklas Ullrich-Kniffka","doi":"10.3238/arztebl.m2025.0001","DOIUrl":"https://doi.org/10.3238/arztebl.m2025.0001","url":null,"abstract":"","PeriodicalId":11258,"journal":{"name":"Deutsches Arzteblatt international","volume":"122 6","pages":"170-171"},"PeriodicalIF":6.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Applying the European Urinalysis Guideline.","authors":"Nicolas von Ahsen","doi":"10.3238/arztebl.m2024.0186","DOIUrl":"https://doi.org/10.3238/arztebl.m2024.0186","url":null,"abstract":"","PeriodicalId":11258,"journal":{"name":"Deutsches Arzteblatt international","volume":"122 6","pages":"m1021"},"PeriodicalIF":6.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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