Management of severe immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors
Menée à partir de données portant sur 3 211 patients atteints d'un cancer du poumon non à petites cellules de stade avancé (âge médian : 67 ans), cette étude analyse la prise en charge des événements immunitaires indésirables sévères induits par les inhibiteurs de point de contrôle immunitaire (hospitalisations, recours aux services des urgences, arrêt du traitement, décès) et évalue l'impact de cette prise en charge sur la survie sans progression et la survie globale
Résumé en anglais
Background: Immune checkpoint inhibitors (ICIs) are associated with severe immune-related adverse events (s-irAEs) that result in hospitalization, emergency department (ED) visits, treatment discontinuation, or death. This study examined the impact of s-irAEs and their earliest management strategies on clinical outcomes in advanced non-small cell lung cancer (NSCLC).
Methods: Data were derived from ConcertAI Patient360 NSCLC, a US-based electronic medical record database, between January 2012 and May 2021. Eligible patients had advanced NSCLC and received ICI-containing therapy. s-irAEs and management actions were abstracted from unstructured EHR data from ICI initiation through the earliest of 100 days after ICI discontinuation, start of a non-ICI-containing regimen, loss to follow up, end of study period, or death. Multivariable Cox regression analysis was used to evaluate the association between s-irAEs and their earliest management strategies, and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS).
Results: The study included 3211 patients. Median (IQR) age was 67 (60-73) years, and 44.9% were female. Most patients (61.6%) initiated ICIs as first-line therapy; half (50.1%) initiated ICIs as monotherapy, with nivolumab monotherapy (29.5%) as the most common initial ICI-containing regimen in any line. Overall, 8.6% of patients experienced s-irAEs, most often diarrhea (3.5%), pneumonitis (1.4%), and rash (1.3%). Among patients who experienced at least one s-irAEs, over half (57.4%) were hospitalized, and 71.8% were treated with corticosteroids, any time after the occurrence of their first s-irAEs. Median rwPFS was 4.9 (95%CI, 4.6-5.2) months, and median rwOS was 13.6 (12.6-14.7) months from ICI initiation. rwPFS and rwOS were comparable between patients with s-irAEs vs patients without s-irAEs when s-irAEs were first managed with anti-cancer treatment interruptions. Patients with s-irAEs had a 53% (22.3%-91.4%) higher risk of death than patients without s-irAEs when s-irAEs initially required corticosteroids or other immunosuppressants, and a 61% (37.9%-87.9%) higher risk of death when s-irAEs first required hospitalization or ED admission.
Conclusion: The impact of s-irAEs on clinical outcomes may depend on the initial intervention required to manage the adverse event. s-irAEs were associated with worse outcomes when they initially required hospital/ED admission, corticosteroids, or other immunosuppression.
