title: Treatment Patterns and Overall Survival Associated with First-Line Systemic Therapy for Patients with Advanced Non-Small Cell Lung Cancer.
abstract: BACKGROUND
  A variety of regimens are used as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC), which may include combination regimens and single agents, depending on histology, molecular profile, and performance status.
  
  
  OBJECTIVE
  To describe the types of first-line therapies and compare overall survival between therapies used for patients with advanced NSCLC in an integrated health care system.
  
  
  METHODS
  This retrospective cohort study included patients aged 18 years or older from Kaiser Permanente California with a diagnosis of stage IIIB/IV NSCLC. First systemic treatment date occurred from January 1, 2008, through September 30, 2013. Overall survival was measured as the number of months from initial treatment until death, end of enrollment, or September 30, 2014. Treatment regimens were categorized into 6 mutually exclusive groups: platinum doublets; pemetrexed-based, bevacizumab-based, and pemetrexed + bevacizumab-based combinations; singlets; and tyrosine-kinase inhibitors (TKIs). Survival was compared using Kaplan-Meier curves and adjusted Cox proportional hazard models. Subgroup analyses were performed by age group and by nonsquamous histology.
  
  
  RESULTS
  Of 2,081 patients, approximately half (52.3%) received platinum doublets, followed by TKIs (19.0%), pemetrexed-based regimens (13.4%), bevacizumab-regimens (8.0%), singlets (5.5%), and pemetrexed + bevacizumab-based combinations (1.8%). Median survival was longest for pemetrexed + bevacizumab-based combinations (18.5 months), followed by bevacizumab-based regimens (14.5), TKIs (12.7), pemetrexed-based regimens (10.4), doublets (9.2), and singlets (5.3). There was a significantly reduced risk of mortality for pemetrexed + bevacizumab-based combinations (HR = 0.64; 95% CI = 0.42-0.94) and TKIs (HR = 0.83; 95% CI = 0.73-0.94) compared with doublets. Singlets were associated with an increased risk of mortality (HR = 1.50; 95% CI = 1.22-1.84). Subgroup analysis among patients aged 65 years and over found no significant differences among treatment groups, with the exception of singlets, which were associated with an increased risk of mortality compared with doublets (HR = 1.51; 95% CI = 1.20-1.90). Among patients under aged 65 years, pemetrexed + bevacizumab-based combinations (HR = 0.36; 95% CI = 0.21-0.64) and TKIs (HR = 0.76; 95% CI = 0.59-0.97) were associated with a reduced risk of mortality, and singlets were associated with an increased risk (HR = 1.85; 95% CI = 1.17-2.92).
  
  
  CONCLUSIONS
  In this cohort of patients with advanced NSCLC, patients received a platinum agent with or without bevacizumab or pemetrexed, a TKI, or a single agent. Younger patients (aged < 65 years) receiving bevacizumab + pemetrexed-based combinations had a survival advantage over those receiving platinum doublets, and this finding merits further investigation. Younger patients receiving TKIs also had longer survival. Compared with platinum doublets, we found no survival advantage for older patients receiving bevacizumab or pemetrexed, which suggests that combination therapy of a platinum agent and taxane, such as carboplatin and paclitaxel, could be a reasonable option for older patients who are not candidates for targeted therapy.
  
  
  BACKGROUND
  No outside funding supported this study. Rashid has received past funding from Bristol-Myers Squibb, Astellas, Novartis, and Pfizer. No other authors report any potential financial conflicts of interest. Study concept and design were primarily contributed by Spence and Hui, with input from the other authors. Hui, Spence, and Rashid took the lead in data collection, and data interpretation was performed by Schottinger, Millares, and Spence, assisted by the other authors. The manuscript was written primarily by Spence, along with Chang, and revised by Spence, with input from the other authors.
authors.affiliation: 1 Pharmacy Outcomes Research Group, Kaiser Permanente Southern California, Downey, California.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Spence
authors.affiliation: 4 Pharmacy Outcomes Research Group, Kaiser Permanente Northern California, Oakland, California.
authors.forename: Rita L
authors.initials: RL
authors.lastname: Hui
authors.affiliation: 2 Drug Information Services, Kaiser Permanente Southern California, Downey, California.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: 5 Quality and Clinical Analysis, Kaiser Permanente Southern California, Pasadena, California.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Schottinger
authors.affiliation: 3 Drug Information Services and Pharmacy Outcomes Research, Kaiser Permanente Southern California, Downey, California.
authors.forename: Mirta
authors.initials: M
authors.lastname: Millares
authors.affiliation: 1 Pharmacy Outcomes Research Group, Kaiser Permanente Southern California, Downey, California.
authors.forename: Nazia
authors.initials: N
authors.lastname: Rashid
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001952:Bridged-Ring Compounds; D043823:Taxoids; D000068437:Pemetrexed; C080625:taxane; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel