Real-world efficacy of immune checkpoint inhibitors in PD-L1 negative non-small cell lung cancer: a multicenter retrospective study.

Background: While immune checkpoint inhibitors (ICIs) have significantly improved outcomes for many non-small cell lung cancer (NSCLC) patients, phase 3 trials have shown limited efficacy in programmed cell death ligand 1 (PD-L1) negative subgroups. This study aimed to evaluate the real-world effectiveness and safety of ICI-containing regimens vs. chemotherapy alone in PD-L1 negative NSCLC patients.

Methods: This multicenter, retrospective study analyzed advanced or recurrent NSCLC patients treated between 2015 and 2022 in Japan. From an initial screening of 1,382 patients, we identified patients with PD-L1 negative [tumor proportion score (TPS) <1%] NSCLC. We excluded patients who received molecular targeted therapy, chemoradiotherapy, or had epidermal growth factor receptor (EGFR) mutations. Overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs) were analyzed.

Results: Among the 86 eligible patients identified, 54 received ICI-containing regimens (IC group) and 32 received chemotherapy alone (C group). No significant difference in OS (C vs. IC: median 14.9 vs. 23.8 months, P=0.87) and PFS (C vs. IC: median 6.6 vs. 7.8 months, P=0.20) was observed after covariates adjustment. The overall response rate was higher in the IC group (C vs. IC: 34.4% vs. 50.0%), as was the disease control rate (C vs. IC: 65.6% vs. 81.5%). AEs profiles were similar between groups, with grade 3-4 events occurring in 56.2% of C patients and 59.2% of IC patients. Treatment discontinuation rates due to AEs were comparable (C vs. IC: 21.9% vs. 24.1%, P=0.71).

Conclusions: In this real-world study of PD-L1 negative NSCLC patients, ICI-containing regimens did not demonstrate significantly improved OS or PFS compared to chemotherapy alone. Limited efficacy in this population highlights the need for further investigation and advancement in treatment strategies.