Clinical impact of post-progression survival on overall survival in patients receiving nivolumab monotherapy as a second-line treatment for advanced non-small cell lung cancer

Abstract

Background: The effect of second-line treatment on overall survival (OS) may be affected by subsequent treatment in patients with non-small cell lung cancer (NSCLC); however, in such patients, the correlation between post-progression survival (PPS) and OS is unclear. Our study assessed the correlation of progression-free survival (PFS) and PPS with OS, using individual patient data, in advanced NSCLC patients who were treated with second-line nivolumab monotherapy, METHODS: Between January 2016 and March 2019, we evaluated 92 NSCLC patients who received second-line nivolumab treatment after first-line platinum-based combination chemotherapy. Using individual patient data, the correlations of PFS and PPS with OS were examined.

Results: Linear regression and Spearman rank correlation analysis demonstrated that PPS was strongly correlated with OS (r = 0.85, p < 0.05, R² = 0.75), while PFS was moderately correlated with OS (r = 0.65, p < 0.05, R² = 0.42). Performance status at the beginning of second-line treatment, immune checkpoint inhibitor rechallenge, and the number of treatment regimens used post-progression, after the second-line treatment significantly correlated with PPS (p < 0.05). In advanced NSCLC patients who underwent second-line treatment with nivolumab, in comparison to PFS, there was a stronger correlation between PPS and OS.

Conclusions: Our findings suggest that subsequent treatment for disease progression after a second-line nivolumab treatment had a significant impact on OS.

Keywords: nivolumab; non-small cell lung cancer; survival.

FIGURE 1

Flow chart showing patient selection. Patients received nivolumab monotherapy as a second‐line treatment between January 2016 and March 2019. PFS, progression‐free survival

FIGURE 2

Kaplan–Meier curves of progression‐free survival (PFS) and overall survival (OS). (a) PFS from the start of second‐line nivolumab treatment (all 92 patients received nivolumab as second‐line treatment); median PFS from the start of second‐line chemotherapy: 3.5 months. (b) OS from the start of second‐line nivolumab treatment (all 92 patients received nivolumab as second‐line treatment); median OS: 14.1 months. (c) PFS from the start of second‐line chemotherapy (77 patients with disease progression following second‐line nivolumab monotherapy); median PFS from the start of second‐line nivolumab treatment: 2.4 months. (d) OS from the start of second‐line nivolumab treatment (77 patients with disease progression following second‐line nivolumab monotherapy); median OS: 11.1 months

FIGURE 3

Correlation of progression‐free survival (PFS) and post‐progression survival (PPS) with overall survival (OS) from the start of second‐line nivolumab treatment. (a) Correlation between OS and PFS. (b) Correlation between OS and PPS. *r values represent Spearman's rank correlation coefficients. **R ² values represent linear regression

FIGURE 4

Progression‐free survival (PFS) and post‐progression survival (PPS) in the overall population

FIGURE 5

Kaplan–Meier curves of post‐progression survival (PPS) according to prognostic factors. (a) PPS according to performance status (PS) at the start of second‐line nivolumab treatment (PS 0–1: median, 10.0 months; PS 2–3: median, 1.8 months). (b) PPS according to immune checkpoint inhibitor (ICI) rechallenge after nivolumab treatment (with ICI rechallenge: median, 17.4 months; without ICI rechallenge: median, 4.5 months). (c) PPS according to the number of regimens after disease progression following second‐line nivolumab treatment (no subsequent regimen: median, 2.2 months; one regimen: median, 6.9 months; more than two regimens: median, 17.0 months)