| Added by | amaraver |
|---|---|
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial |
| Creator | Naidoo et al. |
| Author | Jarushka Naidoo |
| Author | Johan F. Vansteenkiste |
| Author | Corinne Faivre-Finn |
| Author | Mustafa Özgüro?lu |
| Author | Shuji Murakami |
| Author | Rina Hui |
| Author | Xavier Quantin |
| Author | Helen Broadhurst |
| Author | Michael Newton |
| Author | Piruntha Thiyagarajah |
| Author | Scott J. Antonia |
| Abstract | 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. |
| Publication | Lung Cancer (Amsterdam, Netherlands) |
| Volume | 166 |
| Pages | 84-93 |
| Date | 2022-04 |
| Journal Abbr | Lung Cancer |
| Language | eng |
| DOI | 10.1016/j.lungcan.2022.02.003 |
| ISSN | 1872-8332 |
| Short Title | Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC |
| Library Catalog | PubMed |
| Extra | PMID: 35245844 |
| Tags | Antibodies, Monoclonal, Carcinoma, Non-Small-Cell Lung, Chemoradiotherapy, clinic, Dermatitis, Exanthema, Humans, Immune checkpoint inhibition, Locally advanced NSCLC, Lung Neoplasms, PACIFIC, Pneumonia, Pneumonitis, Thyroid disorders |
| Date Added | 2022/08/31 - 14:14:07 |
| Date Modified | 2022/08/31 - 14:14:26 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
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