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

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. 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. 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). 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.