Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual
Takashi Shimizu1,2, Eisuke Inoue3, Ryotaro Ohkuma1,4
1Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.
Introduction:
Currently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand-1 (PD-L1) expression (≧50%). Pre-treatment or post-treatment serum soluble PD-L1 (sPD-L1) has been identified as a potential biomarker for assessing ICI efficacy through fixed-point observations. However, existing studies on sPD-L1 changes have produced inconsistent results or have had sample sizes too small to detect clinically meaningful effect sizes. To elucidate the role of sPD-L1, we conducted a collaborative individual patient data meta-analysis of PD-1 inhibitor treatments.
Methods:
We conducted a thorough search of articles in PubMed via Medline, Embase, Scopus, and Cochrane databases from inception to October 20, 2023. Trials were deemed eligible if they contained individual datasets for advanced NSCLC patients, including data on overall survival (OS)/progression-free survival (PFS), as well as pre- and post-treatment sPD-L1 levels after 3-4 cycles of PD-1 inhibitor treatments. Our analysis focused on patients who completed 3-4 cycles of PD-1 inhibitor treatments. The primary outcome measure was OS/PFS, and we assessed changes in sPD-L1 concentration pre- and post-treatment through ELISA analyses.
Results:
From our search, we identified a potential seven trials, encompassing 256 patients. Among these, two trials with 26 patients met the criteria for inclusion in our primary analyses. Over a median follow-up period of 10 months, pooled univariate analysis revealed that increases in sPD-L1 levels during PD-1 inhibitor treatment were not associated with OS (HR = 1.25; CI: 0.52-3.02)/PFS (HR = 1.42; CI: 0.61-3.30) when compared to cases with sPD-L1 decreases. Subgroup analyses indicated that the impact of sPD-L1 changes on overall mortality/progression-related mortality remained consistent regardless of gender, age, or the type of treatment (nivolumab or pembrolizumab).
Conclusion:
Our findings suggest that changes in sPD-L1 levels during PD-1 inhibitor treatment do not significantly influence the prognosis of advanced NSCLC patients, regardless of gender, age, or treatment type. Continuous monitoring of sPD-L1 may not offer significant advantages compared to fixed-point observations.
Insights
Changes in serum soluble programmed death-ligand 1 (sPD-L1) during programmed cell death protein-1 (PD-1) inhibitor therapy do not impact outcomes for advanced non-small cell lung cancer (NSCLC) patients. Monitoring sPD-L1 levels offers no significant prognostic advantage.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Research
Background:
- Immune checkpoint inhibitors (ICIs), specifically programmed cell death protein-1 (PD-1) inhibitors, are a first-line treatment for advanced non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression.
- Serum soluble PD-L1 (sPD-L1) has been explored as a potential biomarker for predicting ICI efficacy, but existing studies have yielded inconsistent results due to small sample sizes.
Approach:
- A collaborative individual patient data meta-analysis was conducted, searching multiple databases up to October 20, 2023.
- Included were advanced NSCLC patients receiving PD-1 inhibitor treatment, with data on overall survival (OS)/progression-free survival (PFS) and pre- and post-treatment sPD-L1 levels.
- Two trials with 26 patients met the inclusion criteria for primary analysis.
Key Points:
- Pooled analysis of 26 patients over a median follow-up of 10 months found no association between increased sPD-L1 levels and OS or PFS.
- Subgroup analyses confirmed that sPD-L1 changes did not significantly affect mortality outcomes across different genders, ages, or treatments (nivolumab/pembrolizumab).
Conclusions:
- Changes in sPD-L1 levels during PD-1 inhibitor therapy do not significantly predict prognosis in advanced NSCLC patients.
- Continuous monitoring of sPD-L1 offers no discernible advantage over fixed-point observations for assessing treatment efficacy.
