Terry L Ng1, Derek E Smith2, Rao Mushtaq3, Tejas Patil3, Anastasios Dimou3, Shuo Yang4, Qian Liu4, Xuefei Li4, Caicun Zhou4, Robert T Jones5, Megan M Tu6, Flora Yan7, I Alex Bowman7, Stephen V Liu8, Siera Newkirk9, Joshua Bauml9, Robert C Doebele3, Dara L Aisner10, Dexiang Gao2, Shengxiang Ren4, D Ross Camidge3. 1. Division of Medical Oncology, University of Colorado, Aurora, Colorado. Electronic address: terry.ng@ucdenver.edu. 2. Department of Pediatrics, Cancer Center Biostatistics Core, University of Colorado and Children's Hospital Colorado, Aurora, Colorado. 3. Division of Medical Oncology, University of Colorado, Aurora, Colorado. 4. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 5. Department of Pharmacology, University of Colorado, Aurora, Colorado. 6. Department of Surgery, University of Colorado, Denver, and University of Colorado Comprehensive Cancer Center, Aurora, Colorado. 7. University of Texas at Southwestern, Dallas, Texas. 8. Georgetown University, Washington, DC. 9. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 10. University of Colorado, Department of Pathology, Aurora, Colorado.
Abstract
INTRODUCTION: This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. METHODS: Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002-April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers. RESULTS: Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group. CONCLUSIONS: The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC.
INTRODUCTION: This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. METHODS: Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002-April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers. RESULTS: Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLCpatients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group. CONCLUSIONS: The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC.
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Authors: Andrew Dunbar; Kelly L Bolton; Sean M Devlin; Francisco Sanchez-Vega; Jianjiong Gao; Jodi V Mones; Jonathan Wills; Daniel Kelly; Mirko Farina; Keith B Cordner; Young Park; Sirish Kishore; Krishna Juluru; Neil M Iyengar; Ross L Levine; Ahmet Zehir; Wungki Park; Alok A Khorana; Gerald A Soff; Simon Mantha Journal: Blood Date: 2021-04-15 Impact factor: 25.476