期刊
LUNG CANCER
卷 166, 期 -, 页码 84-93出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2022.02.003
关键词
Locally advanced NSCLC; Pneumonitis; Immune checkpoint inhibition; Thyroid disorders; Chemoradiotherapy; PACIFIC
资金
- AstraZeneca [2014-000336-42, NCT02125461]
- [EudraCT: 2014-000336-42]
This study provides detailed characterization and analysis of immune-mediated adverse events (imAEs) in patients with non-small cell lung cancer treated with the PACIFIC regimen. The incidence of immune-mediated pneumonitis and non-pneumonitis imAEs was low, but higher in patients receiving durvalumab. Most imAEs occurred within 3 months after starting durvalumab, but were well managed with appropriate clinical intervention.
Introduction: Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis, were reported in approximately 25% of patients in the placebo-controlled, phase III PACIFIC trial of durvalumab monotherapy (for up to 12 months) in patients with unresectable, stage III NSCLC and no disease progression after concurrent chemoradiotherapy; only 3.4% of patients experienced grade 3/4 imAEs. With broad application of the PACIFIC regimen (consolidation durvalumab after chemoradiotherapy), now standard-of-care in this setting, there is a need to better characterize the occurrence of imAEs with this regimen. Methods: We performed descriptive, post-hoc, exploratory analyses to characterize the occurrence of imAEs (pneumonitis and non-pneumonitis) in PACIFIC in terms of: incidence, severity, and timing; clinical management and outcomes; and associations between the occurrence of imAEs and (1) all-cause AEs and (2) baseline patient, disease, and treatment characteristics. Results: Any-grade immune-mediated pneumonitis (9.4%) and non-pneumonitis imAEs (10.7%) occurred infrequently and were more common with durvalumab versus placebo. Grade 3/4 immune-mediated pneumonitis (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 imAEs with durvalumab were thyroid disorders, dermatitis/ rash, and diarrhea/colitis. Dermatitis/rash had 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 managed with administration of systemic corticosteroids, administration of endocrine replacement therapy, and interruption/discontinuation of durvalumab. Time elapsed from completion of prior radiotherapy to trial randomization (< 14 vs. >= 14 days) did not impact either incidence or severity of imAEs. Durvalumab had a manageable safety profile broadly irrespective 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.
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