Association between pretreatment emotional distress and survival outcomes in patients with advanced non–small-cell lung cancer: An individual patient data meta-analysis of 4632 patients in 7 trials.

Abstract

8546 Background: Emotional distress (ED) associated with worse survival outcomes in patients with melanoma and non-small-cell lung cancer treated with immune checkpoint inhibitors (ICIs). However, several preclinical studies suggest the association between stress and cancer treatment extends beyond ICIs alone. Here we used an individual patient data (IPD) meta-analysis of 4632 patients in 7 trials and a Kaplan-Meier analysis to verify broader connection between ED and survival outcomes in NSCLC patients. Methods: We searched Vivli data-sharing platform for studies which reported clinical trials of advanced NSCLC patients treated with atezolizumab and used the EORTC QLQ-C30 scale to define ED status of patients. Integrating IPD and grouped them into four groups according to ED status and treatment, Kaplan-Meier analysis was conducted to estimate median overall survival (mOS) and progression-free survival (mPFS) for each group. Next we utilized the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% CIs for OS and PFS of each trials. The IPD meta-analysis was conducted to generate summary estimates of results of aggregated data. Results: Among a total of 4632 participants, 2753 (59.43%) received first-line treatment; 3162 (68.26%) received ICIs; 1802 (38.90%) classified as ED and 2830 (61.10%) classified as non-ED. Kaplan-Meier analysis indicate that ED patients associate with worse survival outcomes, regardless of ICIs or chemotherapy (CT) (HROS=1.21, p=0.01; HRPFS=1.19, p=0.01). Compared with non-ED, ED patients had worse OS in both ICIs ( ED vs non-ED, mOS, 13.34 m vs 16.07 m; p=0.01; HR, 1.21 [1.09-1.34]) and CT (ED vs non-ED, mOS, 12.02 m vs 13.93 m; p=0.01; HR, 1.19 [1.04-1.37]). IPD meta-analysis indicate that the ED group exhibited worse OS outcome (HR=1.18 [1.07-1.30], p=0.01). Subgroup analysis confirmed this association in both ICIs (HR=1.18 [1.04-1.34], p=0.01) and CT groups (HR=1.18 [1.00-1.39], p=0.05). Excluded clinical trials which PFS not primary outcome, and investigated the association with ED and PFS in first-line clinical trials. Similarly, Kaplan-Meier analysis show ED patients had worse PFS regardless of ICIs (mPFS, 5.52 m vs 5.58 m; p=0.01; HR, 1.19 [1.06-1.33]) or CT (mPFS, 5.55 m vs 5.59 m; p=0.06; HR, 1.17 [0.99-1.37]). IPD meta-analysis of PFS also supported results above (HR=1.15 [1.03-1.28], p=0.02). Conclusions: The NSCLC patients with ED are significantly associated with adverse survival outcomes regardless of CT or ICIs. The findings recommend the implementation of ED status assessment in clinical practice for NSCLC patients to improve their survival outcomes.