“STRESS-LUNG-1 highlights the crucial role of addressing [emotional distress] and optimizing mental health in [patients with] cancer. This study introduces the first ‘psycho-biomarker’ to predict the efficacy of ICIs in NSCLC,” according to the editorial authors.
Pretreatment emotional distress may significantly correlate with worse clinical efficacy following immune checkpoint inhibitor (ICI) use in patients with advanced non–small cell lung cancer (NSCLC), supporting a need for an integrative care approach in this population, according to an editorial commentary published in Translational Lung Cancer Research.1
According to the authors of the editorial, data from the prospective observational STRESS-LUNG-1 study (NCT05477979) establish “compelling evidence” of this link between emotional distress and clinical outcomes in this population. Investigators previously published findings from STRESS-LUNG-1 in Nature Medicine.2
With a data cutoff of November 30, 2023, and a median follow-up of 16.0 months (95% CI, 14.0-18.0), the median progression-free survival (PFS) was 9.2 months (95% CI, 7.0-11.4) following ICI therapy across the overall population, 7.9 months (95% CI, 6.2-9.7) among patients who exhibited emotional distress, and 15.5 months (95% CI, 7.8-23.2) in those without emotional distress. The median PFS was significantly shorter among patients with emotional distress (HR, 1.73; 95% CI, 1.23-2.43; P = .002), and this association persisted across various patient subgroups.
Additional data showed an objective response (ORR) of 54.6% (95% CI, 48.1%-61.1%) across all patients, 46.8% (95% CI, 37.6%-56.1%) among those with emotional distress, and 62.1% (95% CI, 53.2%-70.9%) in those without. Those with emotional distress experienced significantly lower odds of achieving a response vs those without emotional distress (OR, 0.54; 95% CI, 0.32-0.91; P = .022).
Regarding overall survival (OS), patients in the emotional distress cohort had a higher risk of death from any cause (HR, 1.82; 95% CI, 1.12-2.97; P = .016). In those with and without emotional distress, respectively, the OS rates were 70.4% vs 80.8% at 1 year and 46.5% vs 64.9% at 2 years.
Quality of life (QOL) data showed that patients with emotional distress experienced lower global health scores as well as worse measures for individual functional domains related to physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning. Those with emotional distress also had worse symptoms of fatigue, pain, dyspnea, insomnia, loss of appetite, and constipation.
“STRESS-LUNG-1 highlights the crucial role of addressing [emotional distress] and optimizing mental health in [patients with] cancer. This study introduces the first ‘psycho-biomarker’ to predict the efficacy of ICIs in NSCLC,” Shannon Zhang, a hematology and oncology fellow in the Division of Hematology/Oncology of the Department of Medicine at University of California Irvine, wrote with coauthors in the editorial.1 “Moving forward, multi-center and global studies involving diverse populations are essential.”
In cohort 1 of the STRESS-LUNG trial, otherwise known as the STRESS-LUNG-1 cohort, investigators assessed patients with advanced NSCLC who received PD-1 and PD-L1 inhibitors, which included agents like pembrolizumab (Keytruda), atezolizumab (Tecentriq), and camrelizumab. The study’s primary end point was investigator-assessed PFS. Secondary end points included ORR, OS, and QOL.
Eligible patients were 18 years or older; had histologically confirmed NSCLC; had unresectable, locally advanced, metastatic, or recurrent stage IIB to IV disease; had an ECOG performance of 0 or 1; had at least 1 measurable lesion per RECIST v1.1 guidelines; and underwent treatment at the Second Xiangya Hospital of Central South University in Hunan China. Investigators assessed emotional distress in patients at baseline before initiation of ICI therapy, with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) questionnaires used to evaluate symptoms of depression and anxiety, respectively.
The median patient age was 63 years (IQR, 57-69) in the overall population (n = 227), 63.5 years (range, 57-68) in those without emotional distress (n = 116), and 63 years (IQR, 57-69) in those with emotional distress. In those with and without emotional distress, respectively, most patients had an ECOG performance status of 1 (83.8% vs 78.4%), current or former smoking history (83.8% vs 90.5%), stage IV disease (64.0% vs 52.6%), treatment with ICIs as part of a combination regimen (92.8% vs 96.6%), and no brain or liver metastases (84.7% vs 87.9%).
“We urge oncologists to assess mental health from the initial evaluation and throughout treatment. Early involvement of multidisciplinary support teams, including palliative care, psychologists, psychiatrists, and social workers, is vital for improving outcomes,” the editorial authors wrote.1 “Further research is needed to determine if treating [emotional distress] can significantly enhance overall outcomes, given the potential for prolonged resolution times.”
References
- Zhang S, Wang S, Arter ZL. Emotional distress: the hidden barrier to immunotherapy success in advanced non-small cell lung cancer. Transl Lung Cancer Res. 2025;14(5):1877–1881. doi:10.21037/tlcr-2025-31
- Zeng Y, Hu CH, Li YZ, et al. Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer. Nat Med. 2024;30(6):1680-1688. doi:10.1038/s41591-024-02929-4