1843MO - The effect of chronic psychological stress on the efficacy of first-line therapy of ICIs in advanced NSCLC (STRESS-LUNG-1 trial)

Background

Immune checkpoint inhibitors (ICIs) achieved breakthroughs in advanced non-small cell lung cancer (NSCLC). Chronic psychosocial stress manifests as depression and anxiety symptoms and is common among NSCLC patients. It activates the HPA axis and sympathetic nervous system, which impairs organic immunity and induces an immunosuppressive tumor microenvironment. We aim to investigate the role of chronic psychosocial stress on the efficacy of ICIs.

Methods

The STRESS-LUNG-1 study is a multicenter prospective observational trial (NCT05477979). Stage ⅢB-Ⅳ NSCLC treated with first-line therapy of ICIs were enrolled. The patients' stress status was assessed using PHQ-9 and GAD-7 scales. The last follow-up date was March 1, 2023. Prediction models integrating psycho-biological factors to predict efficacy was established.

Results

A total of 166 NSCLC patients were enrolled with 53.6% of patients classified as stressed. The baseline characteristics between stressed and non-stressed groups were well-balanced. With the median follow-up of 11.5 months, the stressed group had a lower ORR (38.8% vs 68.4%, p<0.001) and a worse median PFS (7.9 vs 15.5 months; p=0.028). The stress group had a lower 1-year (69.0% vs 91.9%; p=0.001) and 2-year survival rate (50.6% vs 71.8%; p=0.092). Patients in the stress group demonstrated multidimensional detriments of quality of life (QoL). Chronic psychological stress was the independent prognostic factor for ORR (HR=3.93; p<0.001), PFS (HR=1.59; p=0.038), and OS (HR=3.16; p=0.005). A negative correlation was observed between the degree of stress and the efficacy. The stressed group had higher plasma epinephrine (160.97 vs 122.94 pg/ml, p=0.029) and serum cortisol levels (445.05 vs 382.10 nmol/L, p=0.037). Notably, an integrated model including stress status, stage, and PD-L1 expression demonstrated superior efficiency in predicting PFS (AUC=0.810) and OS (AUC=0.865) than using psychological and biological factors alone.

Conclusions

Chronic psychological stress was associated with poor efficacy of ICIs and QoL in advanced NSCLC. Combining psychological with biological factors may represent a useful psycho-biomarker able to predict the clinical response to ICIs.

Clinical trial identification

NCT05477979.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

1) National Natural Science Foundation of China (Grant No. 82272806); 2) Natural ScienceFoundation of Hunan Province for Excellent Young Scholars (Grant No. 2021JJ20088); 3) Central South University Research Programme of Advanced Interdisciplinary Studies (Grant No. 2023QYJC039).

Disclosure

All authors have declared no conflicts of interest.