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

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.

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.

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.

(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.