{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:11:58Z","timestamp":1792008718430,"version":"4.4.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              <jats:italic>KRAS<\/jats:italic>\n              is the most commonly mutated driver oncogene in non\u2013small cell lung cancer (NSCLC). Sotorasib and adagrasib, KRAS\n              <jats:sup>G12C<\/jats:sup>\n              inhibitors, have been granted accelerated US approval; however, hepatotoxicity is a common side effect with higher rates in patients treated with sotorasib proximal to checkpoint inhibitor (CPI) therapy. The aim of this study was to assess the feasibility and safety of adagrasib after discontinuation of sotorasib because of treatment-related grade 3 hepatotoxicity through real-world and clinical cases.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              Medical records from five patients treated in real-world settings were retrospectively reviewed. Patients had locally advanced or metastatic\n              <jats:italic>KRAS<\/jats:italic>\n              <jats:sup>G12C<\/jats:sup>\n              -mutated NSCLC and received adagrasib after sotorasib in the absence of extracranial disease progression. Additional data were collected for 12 patients with\n              <jats:italic>KRAS<\/jats:italic>\n              <jats:sup>G12C<\/jats:sup>\n              -mutated NSCLC enrolled in a phase Ib cohort of the KRYSTAL-1 study and previously treated with sotorasib. The end points associated with both drugs included timing and severity of hepatotoxicity, best overall response, and duration of therapy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>All patients were treated with CPIs followed by sotorasib (initiated 0-64 days after CPI). All five real-world patients experienced hepatotoxicity with sotorasib that led to treatment discontinuation, whereas none experienced treatment-related hepatotoxicity with subsequent adagrasib treatment. Three patients from KRYSTAL-1 transitioned from sotorasib to adagrasib because of hepatotoxicity; one experienced grade 3 ALT elevation on adagrasib that resolved with therapy interruption and dose reduction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              Adagrasib may have a distinct hepatotoxicity profile from sotorasib and is more easily combined with CPIs either sequentially or concurrently. These differences may be used to inform clinical decisions regarding an initial KRAS\n              <jats:sup>G12C<\/jats:sup>\n              inhibitor for patients who recently discontinued a CPI or experience hepatotoxicity on sotorasib.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po.23.00644","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T19:59:41Z","timestamp":1712347181000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Adagrasib Treatment After Sotorasib-Related Hepatotoxicity in Patients With\n            <i>KRAS<\/i>\n            <sup>G12C<\/sup>\n            -Mutated Non\u2013Small Cell Lung Cancer: A Case Series and Literature Review"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3606-827X","authenticated-orcid":true,"given":"Jia","family":"Luo","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"},{"name":"Brigham and Women's Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-1773","authenticated-orcid":true,"given":"Narjust","family":"Florez","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"},{"name":"Brigham and Women's Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Donnelly","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, MI"},{"name":"Virginia Cancer Specialists, Fairfax, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6207-9461","authenticated-orcid":true,"given":"Yanyan","family":"Lou","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Jacksonville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4793-9928","authenticated-orcid":true,"given":"Kevin","family":"Lu","sequence":"additional","affiliation":[{"name":"Moores Cancer Center at UC San Diego Health, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"Ma","sequence":"additional","affiliation":[{"name":"Penn State Cancer Institute, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1303-0447","authenticated-orcid":true,"given":"Alexander I.","family":"Spira","sequence":"additional","affiliation":[{"name":"Virginia Cancer Specialists, Fairfax, VA"},{"name":"NEXT Oncology, Fairfax, VA"},{"name":"US Oncology Research, The Woodlands, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Ryan","sequence":"additional","affiliation":[{"name":"Mirati Therapeutics, Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-0963","authenticated-orcid":true,"given":"Hatim","family":"Husain","sequence":"additional","affiliation":[{"name":"Moores Cancer Center at UC San Diego Health, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1638"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-022-00922-w"},{"key":"e_1_3_6_4_2","unstructured":"US Food and Drug Administration: LUMAKRAS prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214665s000lbl.pdf"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0201"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2030638"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.120858"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00780-4"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02225-w"},{"key":"e_1_3_6_10_2","unstructured":"US Food and Drug Administration: KRAZATI prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/216340s000lbl.pdf"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00221-0"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2023.05.013"},{"key":"e_1_3_6_13_2","article-title":"Clinical and genomic features of response and toxicity to sotorasib in a real-world cohort of patients with advanced KRAS G12C-mutant non-small cell lung cancer","author":"Thummalapalli R","unstructured":"Thummalapalli R, Bernstein E, Herzberg B, et al: Clinical and genomic features of response and toxicity to sotorasib in a real-world cohort of patients with advanced KRAS G12C-mutant non-small cell lung cancer. 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