The Social Security Death Index (Social Security Administration’s [SSA] Master Death File) was used to supplement documented vital status [8]. All data access, use, and reporting were conducted in a manner compliant with the Health Insurance Portability and Accountability Act, ensuring that confidentiality and privacy of patients were maintained. In addition, the use of patient data for this study was approved by an independent, central institutional Angiogenesis inhibitor review board. The target population was patients with advanced nonsquamous NSCLC who initiated first-line treatment

between January 2006 and December 2009 (i.e., study enrollment period). To be eligible for analysis, patients were required to meet the following criteria: (1) be at least 18 years of age, (2) have at least one International Classification of see more Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for lung cancer (162.2, 162.3, 162.4, 162.5, 162.8,

162.9, 197.0, or 231.2) along with documented advanced disease (stage IIIB/IV or early stage with evidence of progression to advanced disease), and (3) initiate first-line chemotherapy with or without targeted therapy (i.e., Pem/Plat, Pac/Carbo, or Pac/Carbo/Bev after documentation of advanced disease). The date of first-line treatment was defined as the index date. Patients were excluded based on the following criteria: (1) receiving care for another primary cancer during the study period, (2) squamous cell histology, (3) enrollment in clinical trials during the study period, (4) follow-up time of less than 1 year and no evidence of disease progression/death. Eligible patients were placed into the following cohorts based on first-line treatment initiation: (1) 3-oxoacyl-(acyl-carrier-protein) reductase Pem/Plat, (2) Pac/Carbo doublet, or (3) Pac/Carbo/Bev triplet. To mitigate any potential bias due to differences in patient characteristics, a matching strategy was employed. Patients in each cohort were placed into specific strata based on five key variables listed in Table 1. Within each strata (e.g.,

index year 2007, advanced stage IV, male, performance status score of 1, and age bracket 40–49), a Pem/Plat patient was randomly matched to one Pac/Carbo patient and one Pac/Carbo/Bev patient. Patients were followed for 1 year after the index date to capture the outcomes of interest. The primary effectiveness measures included progression-free survival (PFS) and overall survival (OS). Progression was identified and/or verified through chart review and was defined as a treatment change indicative of disease progression or documented disease progression. In cases of uncertainty of disease progression, a clinical expert (Dr. Mark Green) confirmed progression status. Date of death was captured from the SSA Death Index Master File in combination with date of death in the ION EMR data.