title: Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses.
abstract: OBJECTIVE
  To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) trials.
  
  
  METHODS
  We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies.
  
  
  RESULTS
  In the trial-level analysis, the association between PFS and ORR was strong (R(2) = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R(2) = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R(2) = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43).
  
  
  CONCLUSIONS
  On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect.
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD. Gideon.Blumenthal@fda.hhs.gov.
authors: Gideon M
authors: GM
authors: Blumenthal
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Stella W
authors: SW
authors: Karuri
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Hui
authors: H
authors: Zhang
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Lijun
authors: L
authors: Zhang
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Sean
authors: S
authors: Khozin
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Dickran
authors: D
authors: Kazandjian
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Shenghui
authors: S
authors: Tang
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Rajeshwari
authors: R
authors: Sridhara
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Patricia
authors: P
authors: Keegan
authors: All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.
authors: Richard
authors: R
authors: Pazdur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016014:Linear Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult