Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: a post-hoc analysis of the PACIFIC trial
Menée à partir des données d'un essai de phase III évaluant l'efficacité du durvalumab chez des patients atteints d'un cancer du poumon non à petites cellules non résécable, cette étude analyse l'incidence et la sévérité des événements indésirables à médiation immunitaire (dont les pneumopathies) en lien avec le traitement anticancéreux
Introduction : Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis,were reported in
∼
25% of patients in the placebo-controlled, phase III PACIFIC trialof durvalumab monotherapy (≤12 months) in patients with unresectable, stage III NSCLCand no disease progression after concurrent chemoradiotherapy; only 3.4% of patientsexperienced grade 3/4 imAEs. With broad application of the PACIFIC regimen (consolidation durvalumab after chemoradiotherapy), now standard-of-care in this setting, there isa need to better characterize the occurrence of imAEs with this regimen. Methods : We performed descriptive, post-hoc, exploratory analyses to characterize the occurrenceof imAEs (pneumonitis and non-pneumonitis) in PACIFIC in terms of: incidence, severity,and timing; clinical management and outcomes; and associations between the occurrenceof imAEs and (1) all-cause AEs and (2) baseline patient/disease/treatment characteristics. Results : Any-grade immune-mediated pneumonitis (9.4%) and non-pneumonitis imAEs (10.7%) occurredinfrequently and were more common with durvalumab versus placebo. Grade 3/4 immune-mediatedpneumonitis (1.9%) and non-pneumonitis imAEs (1.7%) were uncommon with durvalumab,as were fatal imAEs (0.8%; all pneumonitis). The most common non-pneumonitis imAEswith durvalumab were thyroid disorders, dermatitis/rash, and diarrhea/colitis. Dermatitis/rashhad the shortest time to onset (from durvalumab initiation), followed by pneumonitis;dermatitis/rash had the longest time to resolution, followed by thyroid disorders.Most patients with immune-mediated pneumonitis (78.4%) and non-pneumonitis imAEs (56.3%)had these events occur ≤3 months after initiating durvalumab. ImAEs were well managedwith administration of systemic corticosteroids, administration of endocrine replacementtherapy, and interruption/discontinuation of durvalumab. Time elapsed from completionof prior radiotherapy to trial randomization (<14 vs ≥14 days) did not impact eitherincidence or severity of imAEs. Durvalumab had a manageable safety profile broadlyirrespective of whether patients experienced imAEs. Conclusion : The risk of imAEs should not deter use of the PACIFIC regimen in eligible patients,as these events are generally well managed through appropriate clinical intervention.
Lung Cancer 2022