The association between emotional distress prior to receiving immune checkpoint inhibitors and overall survival among patients with cancer: A population-based study.

Abstract

12106 Background: Immune checkpoint inhibitors (ICIs) are widely used across cancer care. Emerging evidence from smaller studies links pretreatment emotional distress (ED) to poorer outcomes in patients with melanoma and non-small cell lung cancer undergoing ICIs due to changes in inflammatory states but large-scale studies are lacking. We conducted a population-level retrospective cohort study to assess the impact of pre-treatment ED on overall survival (OS) across solid tumor patients treated with ICIs. Methods: Using population-level administrative data, a cohort of patients with cancer, age 18 years or older, who received at least one dose of an ICI between June 2012 to October 2018 in Ontario, Canada, were identified using systemic therapy databases. Databases were deterministically linked to obtain socio-demographic, clinical co-variates, pre-treatment ED levels, and overall survival. ED was defined as having the sum of the Edmonton Symptom Assessment Scale (ESAS) anxiety and depression score ≥ 4. Multivariable Cox proportional hazard models assessed the association between ED and OS, adjusted for age, sex, body mass index, history of autoimmune conditions, cancer centre facility level, comorbidity score, and hospitalization within 60 days prior to starting ICI. Results: Among the 3237 patients who received ICIs and completed the ESAS prior to ICI treatment, most were male (58%), median age 67 years (IQR 59-74), the median combined ESAS anxiety and depression score was 3 (IQR 0-7); 45% had pre-treatment ED. The majority had lung cancer (49%), melanoma (37%) or renal cancer (9%), and were either treated with nivolumab (42%), pembrolizumab (36%) or ipilimumab (19%). Median OS was 330 days. Pre-ICI treatment ED was associated with poorer OS (aHR = 1.23, 95% CI [1.12–1.34] P < 0.0001) and when analyzed as a continuous variable, a higher combined ESAS anxiety and depression score was associated with poorer OS (aHR = 1.02 per 1 unit increase, 95% CI [1.01-1.03] P < 0.0001). Pre-treatment ED was associated with poorer OS for both males (aHR males = 1.27, 95% CI [1.12–1.43] P = 0.0001) and females (aHR females = 1.18, 95% CI [1.03–1.36] P = 0.02). Among disease sites, ED was associated with reduced OS among patients with lung cancer (aHR = 1.33, 95% CI [1.17–1.51] P < 0.0001) and showed a similar but non-significant trend among patients with melanoma (aHR = 1.14, 95% CI [0.98–1.32] P = 0.09); while ED not significantly associated OS for patients with renal cancer (aHR = 0.98, P = 0.89). Similar results were observed across sexes and disease sites when evaluating the combined ESAS anxiety and depression score and OS. Conclusions: Among patients receiving ICIs, pretreatment ED is associated with poorer OS. These findings suggest the importance of screening for and addressing ED as a part of routine cancer care, which may potentially influence ICI treatment outcomes.