Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

Media type: E-Article
Title: Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer
Contributor: Daniello, Lea; Elshiaty, Mariam; Bozorgmehr, Farastuk; Kuon, Jonas; Kazdal, Daniel; Schindler, Hannah; Shah, Rajiv; Volckmar, Anna-Lena; Lusky, Fabienne; Diekmann, Leonore; Liersch, Stephan; Faehling, Martin; Muley, Thomas; Kriegsmann, Mark; Benesova, Karolina; Stenzinger, Albrecht; Thomas, Michael; Christopoulos, Petros
imprint: Frontiers Media SA, 2021
Published in: Frontiers in Oncology
Language: Not determined
DOI: 10.3389/fonc.2021.703893
ISSN: 2234-943X
Origination:
Footnote:
Description: <jats:sec><jats:title>Introduction</jats:title><jats:p>PD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>IrAE showed comparable frequencies in stage IV (198/894 or 22%) <jats:italic>vs.</jats:italic> III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy <jats:italic>vs.</jats:italic> chemoimmunotherapy (139/483 <jats:italic>vs.</jats:italic> 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 <jats:italic>vs.</jats:italic> 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 <jats:italic>vs.</jats:italic> 17%, p &lt; 0.001 for NLR dichotomized at 5), better ECOG status (26 <jats:italic>vs.</jats:italic> 18% for 0 <jats:italic>vs.</jats:italic> 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p &lt; 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (&lt;1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean &gt;3 months), and average cumulative prednisone doses &gt;700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 <jats:italic>vs.</jats:italic> 10 months, HR = 0.68, p = 0.009; median OS 37 <jats:italic>vs.</jats:italic> 15 months, HR = 0.40, p &lt; 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p &lt; 0.001).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Approximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.</jats:p></jats:sec>
Access State: Open Access

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