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. 2016 Nov;11(11):1927-1939.
doi: 10.1016/j.jtho.2016.07.017. Epub 2016 Aug 3.

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

Takehito Shukuya  1 , Keita Mori  2 , Joseph M Amann  1 , Erin M Bertino  1 , Gregory A Otterson  1 , Peter G Shields  1 , Satoshi Morita  3 , David P Carbone  4
Affiliations

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

Takehito Shukuya et al. J Thorac Oncol. 2016 Nov.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Alternative end point; Anti–PD-1 antibody; Anti–PD-L1 antibody; Immune checkpoint inhibitor; Non–small cell lung cancer; Overall survival.

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Figures

Figure 1.
Figure 1.
The relationship between median overall survival and either median progression-free survival or response rate in prospective clinical trials using anti–programmed death protein 1/programmed death ligand 1 antibodies in 12 arms. Blue, nivolumab; pink, atezolizumab; brown, pembrolizumab; green, avelumab.
Figure 2.
Figure 2.
The relationship between median overall survival and either median progression-free survival or response rate in prospective clinical trials using docetaxel monotherapy in 23 arms.
Figure 3.
Figure 3.
(A)–(C) Kaplan–Meier curves of overall survival according to tumor response. (D) Kaplan-Meier curves of overall survival in patients who achieved and did not achieve 8-week progression-free status. (E) Kaplan–Meier curves of overall survival in patients who did and did not achieve 16-week progression-free status. (F) Kaplan–Meier curves of overall survival in patients who achieved and did not achieve 24-week progression-free status.
See this image and copyright information in PMC

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