Role of pleural and peritoneal metastasis in immune checkpoint inhibitors efficacy patients with non-small cell lung cancer: real-world data from a large cohort in France

Abstract

Background: Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC.

Methods: We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS).

Results: Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a < 10% chance of yielding a benefit from CKI.

Conclusions: Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLC patients and may be used to avoid CKI monotherapy for such patients.

Keywords: Biomarkers; Checkpoint inhibitors; Immunotherapy; Non-small cell lung cancer.

Fig. 1

Kaplan–Meier curves of overall survival. Kaplan–Meier curves comparing overall survival (OS) according to WHO performance status (a), hepatic (b), bone (c) and pleuroperitoneal (d) metastases

Fig. 2

Kaplan–Meier curves of progression-free survival Kaplan–Meier curves comparing progression-free survival (PFS) according to WHO performance status (a), hepatic (b), bone (c) and pleuroperitoneal (d) metastases

Fig. 3

Kaplan–Meier curves for the composite variable Kaplan–Meier curves comparing overall survival (a) and progression-free survival (b) for the composite variable of performance status ≥ 1 plus presence of pleuroperitoneal metastasis (PS mean performance status)