Abstract and Introduction
Abstract
Background: We sought to estimate the proportion of patients with cancer treated with immune checkpoint inhibitors (ICI) who die soon after starting ICI in the real world and examine factors associated with early mortality (EM).
Methods: We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada. EM was defined as death from any cause within 60 days of ICI initiation. Patients with melanoma, lung, bladder, head and neck, or kidney cancer treated with ICI between 2012 and 2020 were included.
Results: A total of 7126 patients treated with ICI were evaluated. Fifteen percent (1075 of 7126) died within 60 days of initiating ICI. The highest mortality was observed in patients with bladder and head and neck tumors (approximately 21% each). In multivariable analysis, previous hospital admission or emergency department visit, prior chemotherapy or radiation therapy, stage 4 disease at diagnosis, lower hemoglobin, higher white blood cell count, and higher symptom burden were associated with higher risk of EM. Conversely, patients with lung and kidney cancer (compared with melanoma), lower neutrophil to lymphocytes ratio, and with higher body mass index were less likely to die within 60 days post ICI initiation. In a sensitivity analysis, 30-day and 90-day mortality were 7% (519 of 7126) and 22% (1582 of 7126), respectively, with comparable clinical factors associated with EM identified.
Conclusions: EM is common among patients treated with ICI in the real-world setting and is associated with several patient and tumor characteristics. Development of a validated tool to predict EM may facilitate better patient selection for treatment with ICI in routine practice.
Introduction
Immune checkpoint inhibitors (ICI) have dramatically altered the landscape of cancer treatment.[1–7] Despite the promising outcomes seen with the use of ICI, only a portion of patients derive clinical benefit.[8] Therefore, it is crucial to offer these agents to patients most likely to benefit.
Early mortality (EM) following initiation of cancer therapy is well reported in the literature for patients treated with chemotherapy or radiation therapy. However, it is heterogeneously defined and varies substantially, with 30-day and 60-day mortality ranging from 1.7% to 17% and 90-day mortality from 10% to 20%.[9–13] This variation is multifactorial and is related to disease, treatment toxicity, and patient-related factors. Disease-related factors include primary cancer site, tumor stage, and treatment characteristics; and patient-related factors include age, sex, and performance status.[9–13]
Early cross-over of Kaplan-Meier (KM) survival curves seen in clinical trials of ICI suggests that a subpopulation of patients treated with ICI is at higher risk for EM. Potential confounders include older age and comorbidities that may affect survival.[14] Whether EM is the result of disease progression or adverse events associated with ICI is unclear and of interest.[15] An accurate estimate of the proportion of patients who die soon after starting ICI and a better understanding of factors associated with EM after ICI use is needed to identify patients at higher risk for EM. This can help identify patients for earlier interventions to avoid serious toxicities, including early death, and select patients who may derive the most benefit from ICI.
In Ontario, Canada's most populous province with a universal health-care system, ICI were approved for the treatment of patients with select cancers starting in 2012 (Supplementary Table 1, available online). We sought to estimate the proportion of patients who died within 60 days after starting ICI and examine if EM following initiation of ICI is associated with demographic or disease characteristics using a real-world cohort of patients.
J Natl Cancer Inst. 2023;115(8):949-961. © 2023 Oxford University Press
