دورية أكاديمية
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.
| العنوان: | 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. |
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| المؤلفون: | Negrao MV; Department of Thoracic/Head & Neck Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX., Spira AI; Virginia Cancer Specialists, Fairfax, VA.; US Oncology Research, The Woodlands, TX.; NEXT Oncology, Fairfax, VA., Heist RS; Massachusetts General Hospital, Boston, MA., Jänne PA; Dana-Farber Cancer Institute, Boston, MA., Pacheco JM; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO., Weiss J; Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC., Gadgeel SM; Henry Ford Cancer Institute, Detroit, MI., Velastegui K; Mirati Therapeutics, Inc, San Diego, CA., Yang W; Mirati Therapeutics, Inc, San Diego, CA., Der-Torossian H; Mirati Therapeutics, Inc, San Diego, CA., Christensen JG; Mirati Therapeutics, Inc, San Diego, CA., Sabari JK; Perlmutter Cancer Center, New York University Langone Health, New York, NY. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Oct 01; Vol. 41 (28), pp. 4472-4477. Date of Electronic Publication: 2023 Jun 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics , Central Nervous System Neoplasms*/drug therapy , Central Nervous System Neoplasms*/genetics , Neoplasms, Second Primary*, Humans ; Proto-Oncogene Proteins p21(ras)/genetics ; Acetonitriles ; Mutation |
| مستخلص: | Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Patients with Kirsten rat sarcoma viral oncogene homolog ( KRAS )-mutated non-small-cell lung cancer (NSCLC) and untreated CNS metastases have a worse prognosis than similar patients without KRAS mutations. Adagrasib has previously demonstrated CNS penetration preclinically and cerebral spinal fluid penetration clinically. We evaluated adagrasib in patients with KRAS G12C -mutated NSCLC and untreated CNS metastases from the KRYSTAL-1 trial (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), in which adagrasib 600 mg was administered orally, twice daily. Study outcomes included the safety and clinical activity (intracranial [IC] and systemic) by blinded independent central review. Twenty-five patients with KRAS G12C -mutated NSCLC and untreated CNS metastases were enrolled and evaluated (median follow-up, 13.7 months); 19 patients were radiographically evaluable for IC activity. Safety was consistent with previous reports of adagrasib, with grade 3 treatment-related adverse events (TRAEs) in 10 patients (40%) and one grade 4 (4%) and no grade 5 TRAEs. The most common CNS-specific TRAEs included dysgeusia (24%) and dizziness (20%). Adagrasib demonstrated an IC objective response rate of 42%, disease control rate of 90%, progression-free survival of 5.4 months, and median overall survival of 11.4 months. Adagrasib is the first KRAS G12C inhibitor to prospectively demonstrate IC activity in patients with KRAS G12C -mutated NSCLC and untreated CNS metastases, supporting further investigation in this population. |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT03785249 |
| المشرفين على المادة: | 8EOO6HQF8Y (adagrasib) EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) 0 (Acetonitriles) 0 (KRAS protein, human) |
| تواريخ الأحداث: | Date Created: 20230616 Date Completed: 20231023 Latest Revision: 20231024 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10553074 |
| DOI: | 10.1200/JCO.23.00046 |
| PMID: | 37327468 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.23.00046 |