Clinical Research Papers:
Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy
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Anna K. Brady1, Jonathan D. McNeill2, Brendan Judy3, Joshua Bauml4, Tracey L. Evans4, Roger B. Cohen4, Corey Langer4, Anil Vachani5, Charu Aggarwal4
1Department of Medicine, Washington University Medical Center, St. Louis, MO, USA
2Ruth and Raymond Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA
3Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA
4Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
5Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania, Philadelphia, PA, USA
Charu Aggarwal, e-mail: Charu.Aggarwal@uphs.upenn.edu
Keywords: KRAS, non-small cell lung cancer, bevacizumab
Received: May 06, 2015 Accepted: August 24, 2015 Published: September 03, 2015
Introduction: Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20–25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear.
Methods: We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods.
Results: All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58–2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48–1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01).
Conclusions: KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy.
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