Clinical characteristics and survival outcomes of long-term responders for advanced nonsmall cell lung cancer patients with first-line PD-1/PD-L1 inhibitors: a multicenter retrospective study.

Background: Immunotherapy has shown long-term benefits in advanced nonsmall cell lung cancer patients. However, the clinical characteristics, prognosis, and selection of appropriate therapies for long-term responders (LTR) to first-line programmed cell death protein-1/programmed cell death ligand-1 (PD-L1) inhibitors remain undetermined.

Methods: About 413 advanced nonsmall cell lung cancer patients were included from 1 June 2015 to 31 August 2021. It examined clinicopathologic data, overall survival distributions, and treatment strategies involving immune checkpoint inhibitors.

Results: Among the patients, 213 (51.6%) were LTRs. PD-L1 expression ≥50% was observed in 39.1% of LTR patients, higher than in non-LTR patients (21.7%). After propensity score matching, Cox univariable analysis revealed pathological type (hazard ratio [HR] 0.563; 95% confidence interval [CI]: 0.391-0.811; P = .002), bone metastasis (HR 1.820; 95% CI: 1.278-2.590; P = .001), and liver metastasis (HR 2.220; 95% CI: 1.291-3.817; P = .004) as significant predictors of LTR. The pathological type (HR 0.641; 95% CI: 0.441-0.932; P = .020), bone metastasis (HR 1.593; 95% CI: 1.106-2.293; P = .012), and liver metastasis (HR 1.820; 95% CI: 1.046-3.165; P = .034) were significant predictors of LTR in Cox multivariable analysis. Significant difference showed in overall survival (P < .0001) for Pembrolizumab-chemotherapy of lung squamous cell carcinoma in LTR group compared with Sintilimab-chemotherapy.

Conclusions: Nonsquamous cell carcinoma, bone metastasis, and liver metastasis were significant predictors of LTR. LTR patients showed a higher proportion of PD-L1 expression. Compared to Sintilimab-chemotherapy, Pembrolizumab-chemotherapy may be more promising for long-term survival of lung squamous cell carcinoma patients. Key messages What is already known on this topic - Immunotherapy (IO) has demonstrated long-term survival benefits in advanced nonsmall cell lung cancer (NSCLC). However, the clinical characteristics, prognosis, and optimal treatment strategies for long-term responders (LTR) to first-line programmed cell death protein-1/programmed cell death ligand-1 inhibitors remain unclear, necessitating further investigation. What this study adds - This study identifies nonsquamous cell carcinoma, absence of bone metastasis, and absence of liver metastasis as significant predictors of LTR in NSCLC patients. LTR patients exhibit a higher proportion of programmed cell death ligand-1 expression (≥50%). Additionally, Pembrolizumab-chemotherapy shows superior overall survival outcomes for LTR with lung squamous cell carcinoma compared to Sintilimab-chemotherapy. How this study might affect research, practice, or policy - These findings provide critical insights for patient stratification and therapy optimization in NSCLC. The identification of predictive factors and superior therapeutic combinations can guide clinical decision-making, personalized treatment strategies, and inform future research on IO in NSCLC.