title: Relationship between Overall Survival and Response or Progression-Free Survival in Advanced Non-Small Cell Lung Cancer Patients Treated with Anti-PD-1/PD-L1 Antibodies.
abstract: Alternative predictive end points for overall survival (OS), such as tumor response and progression-free survival (PFS), are useful in the early detection of drug efficacy; however, they have not been fully investigated in patients with advanced NSCLC treated with anti-programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies.
  
  
  
  In a systematic review of the reported prospective clinical trials, data for response rate, median PFS, and median OS were extracted from 12 arms in 10 reported clinical trials using anti-PD-1/PD-L1 antibody, and their correlation was investigated. In a retrospective analysis at our institution, OS was compared according to tumor response on 5- to 9-week computed tomography scans and status of being progression-free at 8, 16, and 24 weeks by landmark analysis in 71 patients with advanced NSCLC treated with anti-PD-1/PD-L1 antibodies between 2013 and 2015.
  
  
  
  In a systematic review, moderate correlations between median OS and median PFS (p = 0.120, r = 0.473) and between median OS and response rate (p = 0.141, r = 0.452) were identified using the Spearman correlation coefficient, although these correlations were not statistically significant. In a retrospective analysis of patients treated at our institution, disease control (partial response [PR]/stable disease versus progressive disease/not evaluable), and progression-free status at 8, 16, and 24 weeks significantly predicted OS (Cox proportional hazards model, PR/stable disease versus progressive disease/not evaluable, p = 0.0104, HR = 3.041; 8-week progression-free yes versus no, p = 0.0183, HR = 2.684; 16-week progression-free yes versus no, p = 0.0036, HR = 4.009; and 24-week progression-free yes versus no, p = 0.0002, HR = 12.726).
  
  
  
  Both disease control (PR plus stable disease status) and landmark progression-free survival were correlated with OS, with the longer interval landmark PFS being the best predictor of survival in patients with NSCLC treated with anti-PD-1/PD-L1 antibodies.
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors: Takehito
authors: T
authors: Shukuya
authors: Clinical Trial Coordination Office, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
authors: Keita
authors: K
authors: Mori
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors: Joseph M
authors: JM
authors: Amann
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors: Erin M
authors: EM
authors: Bertino
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors: Gregory A
authors: GA
authors: Otterson
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors: Peter G
authors: PG
authors: Shields
authors: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Satoshi
authors: S
authors: Morita
authors: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio. Electronic address: david.carbone@osumc.edu.
authors: David P
authors: DP
authors: Carbone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: Alternative end point; Anti–PD-1 antibody; Anti–PD-L1 antibody; Immune checkpoint inhibitor; Non–small cell lung cancer; Overall survival