ICI-related adverse events tied to longer survival in metastatic NSCLC

Immune-related adverse events (irAEs) are more likely to develop in metastatic nonsmall cell lung cancer (NSCLC) patients with certain prognostic characteristics, suggests a study. Interestingly, those who develop irAEs benefit from a much longer overall survival (OS) and time to next treatment when mitigating immortal time bias.

“This is the largest contemporary real-world dataset evaluating association between clinically impactful irAEs and survival in metastatic NSCLC,” according to the investigators, led by Sarah Cook from the University of Calgary in Alberta, Canada, who presented the findings at the recent WCLC 2023.

Cook and her team used the Alberta Immunotherapy Database (AID) to explore the association between irAEs and survival in metastatic NSCLC. AID is a provincial multicentre observational cohort containing data from patients receiving immune checkpoint inhibitors (ICIs).

A total of 803 metastatic NSCLC patients treated with ICIs (ie, atezolizumab/nivolumab/pembrolizumab alone or in combination with chemotherapy), agnostic to treatment line between July 2015 and March 2023, were included in this study. Data analysis was then conducted in April 2023.

The association between OS (specified as time from ICI initiation) and irAEs served as the primary endpoint. Only clinically impactful irAEs (defined as mandating ICI delay, cessation, or systemic steroids for toxicity management) were included in the analysis.

To mitigate immortal time bias, Cook and colleagues excluded patients with poor prognosis (survival <3 months) who died prior to developing irAEs from the OS analysis. Finally, they performed adjusted Cox regression analyses to determine the variables associated with OS in the total cohort.

Of the patients treated with ICI, 62 were in combination with chemotherapy. An irAE occurred in 297 patients (37 percent), of whom 90 (11 percent) were hospitalized to manage toxicity. The median time to irAE was 3.4 months, and the most common of which were pneumonitis (n=82, 47 hospitalized), dermatitis (n=62), and colitis (n=42). [WCLC 2023, abstract 1967]

IrAEs were more likely to develop among patients with the following prognostic characteristics: age >60 years (p=0.0463), ECOG 0 (p<0.0001), PDL-1 high (p=0.0458), no bone metastases (p=0.01233), normal haemoglobin (p=0.0282), normal albumin (p<0.0001), normal lactate dehydrogenase (p=0.0074), and derived neutrophil lymphocyte ratio <3 (p<0.0001).

Moreover, development of irAEs showed no association with gender, histology, driver mutation, treatment line, or type of ICI.

When the investigators mitigated immortal time bias (n=611), patients who developed irAE showed a longer OS (median, 23.6 vs 9.8 months; logrank p<0.0001) and longer time to next treatment (median, 18.0 vs 7.3 months; p<0.0001).

OS did not significantly differ between patients whose irAE was treated in a hospital and those in the outpatient setting (median, 20.8 vs 25.6 months; p=0.33). Multivariable analysis confirmed the independent association of irAE incidence with OS in the total cohort (HR, 0.59; p<0.0001).

“ICIs have transformed metastatic NSCLC treatment but may cause severe irAEs,” the investigators said.