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Qian, David; Behera, Madhusmita; Steuer, Conor Ernst; Pakkala, Suchita; Carlisle, Jennifer W; Owonikoko, Taofeek Kunle; Fischer-Valuck, Benjamin Walker; Kesarwala, Aparna Hemant; Bradley, Jeffrey; Curran, Walter J; Ramalingam, Suresh S.; Higgins, Kristin Ann

KRAS G12C mutation associated outcomes among patients with locally advanced non-small cell lung cancer

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  • Medientyp: E-Artikel
  • Titel: KRAS G12C mutation associated outcomes among patients with locally advanced non-small cell lung cancer
  • Beteiligte: Qian, David; Behera, Madhusmita; Steuer, Conor Ernst; Pakkala, Suchita; Carlisle, Jennifer W; Owonikoko, Taofeek Kunle; Fischer-Valuck, Benjamin Walker; Kesarwala, Aparna Hemant; Bradley, Jeffrey; Curran, Walter J; Ramalingam, Suresh S.; Higgins, Kristin Ann
  • Erschienen: American Society of Clinical Oncology (ASCO), 2020
  • Erschienen in: Journal of Clinical Oncology, 38 (2020) 15_suppl, Seite e21079-e21079
  • Sprache: Englisch
  • DOI: 10.1200/jco.2020.38.15_suppl.e21079
  • ISSN: 0732-183X; 1527-7755
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: e21079 Background: Recent progress in targeted therapy includes the demonstration of promising anti-tumor activity and safety of a KRAS inhibitor in patients with advanced malignancies harboring the G12C somatic mutation ( KRASG12C). KRAS mutations are present in one-third of all non-small cell lung cancers (NSCLCs), of which KRASG12C comprises about 40%. In this study we characterize the outcomes of patients with stage III NSCLC who received radiotherapy, stratified by KRASG12C status. Methods: Level 3 data for NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA). Clinical and somatic mutation data were analyzed for the 118 NSCLC patients with stage III disease whose treatment included radiotherapy with or without chemotherapy. Overall survival (OS) and progression-free survival (PFS) were then compared between patients whose tumors possess versus lack KRASG12C using Cox proportional hazards regression. Results: This TCGA cohort study consists of 75 males and 43 females with stage III NSCLC (57 adenocarcinomas and 61 squamous cell carcinomas) enrolled between February 2010 and November 2014. Presence of KRASG12C was detected in 7 patients (6%) and conferred poorer OS (HR 3.14, 95% CI 1.12–8.84, P = 0.030) as well as PFS (HR 3.74, 95% CI 1.46–9.56, P = 0.0059) compared to absence of KRASG12C, with median survival of 9.0 versus 28.9 months and median time to progression of 8.5 versus 16.8 months. All 7 patients with KRASG12C had lung adenocarcinomas (ACs). Inferior survival of patients with KRASG12C persisted on subgroup analyses of AC and KRAS mutation status (Table). Conclusions: Among patients with stage III NSCLC in TCGA treated by radiotherapy, those with KRASG12C had significantly worse OS and PFS. Clinical trial of a KRAS inhibitor is a rational next step toward improving outcomes for this patient population, which has yet to be remarkably impacted by existing precision oncology approaches. [Table: see text]
  • Zugangsstatus: Freier Zugang