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Selecting optimal immunotherapy based on inflammation in stage IV PD-L1 ≥50% gene mutation-negative non-small cell lung cancer: pembrolizumab monotherapy versus combination chemoimmunotherapy.


ABSTRACT:

Background

Systemic inflammation may reduce the efficacy of immunotherapy. For advanced non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥50% and without driver gene mutations, both immunotherapy monotherapy and combination chemoimmunotherapy are considered standard treatment options; however, it remains unclear which treatment is more appropriate depending on the degree of inflammation. This study investigated the impact of inflammation on the effectiveness of pembrolizumab monotherapy versus combination chemoimmunotherapy.

Methods

In this retrospective multicenter cohort study, we included patients with advanced NSCLC from 13 Japanese institutions who received pembrolizumab monotherapy or combination chemoimmunotherapy as first-line treatment between March 2017 and October 2021. The systemic immune-inflammation index (SII) was used as an inflammation marker, with a cutoff value of 1,444 based on previous data. Patients were classified into high (SII ≥1,444) and low (SII <1,444) inflammation groups.

Results

This study included 347 patients with advanced NSCLC: 212 (61.1%) in the pembrolizumab group and 135 (38.9%) in the combination chemoimmunotherapy group. In the high inflammation population, there were no significant differences in progression-free survival (PFS) and overall survival (OS) between the pembrolizumab and combination chemoimmunotherapy groups. In the low inflammation population, PFS and OS were significantly improved in the combination chemoimmunotherapy group compared to the pembrolizumab group [median PFS: 8.8 vs. 16.0 months, hazard ratio (HR) =0.69, P=0.04; median OS: 29.4 vs. not reached (NR), HR =0.55, P=0.007].

Conclusions

In patients with advanced, driver gene mutation-negative NSCLC, high PD-L1 expression (≥50%), and low systemic inflammation, combination chemoimmunotherapy significantly improved PFS and OS compared to pembrolizumab monotherapy.

SUBMITTER: Kunimatsu Y 

PROVIDER: S-EPMC12683408 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature

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Selecting optimal immunotherapy based on inflammation in stage IV PD-L1 ≥50% gene mutation-negative non-small cell lung cancer: pembrolizumab monotherapy versus combination chemoimmunotherapy.

Kunimatsu Yusuke Y   Nishioka Naoya N   Yamada Tadaaki T   Kawachi Hayato H   Tamiya Motohiro M   Negi Yoshiki Y   Goto Yasuhiro Y   Nakao Akira A   Shiotsu Shinsuke S   Tanimura Keiko K   Takeda Takayuki T   Okada Asuka A   Harada Taishi T   Date Koji K   Chihara Yusuke Y   Hasegawa Isao I   Tamiya Nobuyo N   Ishida Masaki M   Kijima Takashi T   Takayama Koichi K  

Translational lung cancer research 20251127 11


<h4>Background</h4>Systemic inflammation may reduce the efficacy of immunotherapy. For advanced non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥50% and without driver gene mutations, both immunotherapy monotherapy and combination chemoimmunotherapy are considered standard treatment options; however, it remains unclear which treatment is more appropriate depending on the degree of inflammation. This study investigated the impact of inflammation on the effecti  ...[more]

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