Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas

Authors

  • Paul K. Paik MD,

    Corresponding author
    1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Cornell Medical College, New York, New York
    • Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065
    Search for more papers by this author
    • Fax: (646) 888-4263

  • Melissa L. Johnson MD,

    1. Division of Hematology/Oncology, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois
    Search for more papers by this author
  • Sandra P. D'Angelo MD,

    1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Cornell Medical College, New York, New York
    Search for more papers by this author
  • Camelia S. Sima MD,

    1. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
    Search for more papers by this author
  • Daphne Ang MD,

    1. Department of Pathology, Oregon Health and Science University, Portland, Oregon
    Search for more papers by this author
  • Snjezana Dogan MD,

    1. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
    Search for more papers by this author
  • Vincent A. Miller MD,

    1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Cornell Medical College, New York, New York
    Search for more papers by this author
  • Marc Ladanyi MD,

    1. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
    Search for more papers by this author
  • Mark G. Kris MD,

    1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Cornell Medical College, New York, New York
    Search for more papers by this author
  • Gregory J. Riely MD, PhD

    1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Cornell Medical College, New York, New York
    Search for more papers by this author

Abstract

BACKGROUND:

The authors previously demonstrated that never-smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking-dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups.

METHODS:

In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods.

RESULTS:

Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P < .0001). Among never-smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype.

CONCLUSIONS:

Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history. Cancer 2012. © 2012 American Cancer Society.

Ancillary