Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis
Open accessAbstract
Purpose Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancer patients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs.Methods We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions.Results Among 195 patients [median (range) age, 63 (30-84) years; 128 men (65.6%), 67 women (34.4%)], irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in irAEs group compared to 2.0 months of no-irAEs group [HR: 0.41 (95% CI 0.3-0.57), P < 0.0001]. Median OS was 17.8 months compared to 4.0 months of no-irAEs group [HR: 0.33 (95% CI 0.23-0.47), P < 0.0001]. IrAEs were significantly associated with improved clinical outcome in 12- and 6-week landmark analysis. Patients who developed ≥ 2 irAEs during treatment (n: 37) had a significantly longer median PFS and OS compared to those with one (n: 48) or none AEs (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2.0, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4.0, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with PFS [HR: 0.48 (95% CI 0.34-0.67), P < 0.0001] and OS [HR: 0.38 (95% CI 0.26-0.56), P < 0.0001].Conclusion In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLC patients treated with nivolumab monotherapy in landmark and multivariable models. Patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE further suggesting a mechanistic association between irAEs and immunotherapy efficacy.
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A 12-week landmark analysis confirmed the same statistically significant differences between patients who did and did not develop IRAEs.
“A 12-week landmark analysis confirmed the same statistically significant differences between patients who did and did not develop IRAEs.”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [34]
In that analysis, patients who experienced IRAEs had statistically significant improvements in ORR (43.5% vs 10%, p < .001).
“Patient who experienced IRAEs had statistically significant improvements in ORR (43.5% vs 10%, p < .001)”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [34]
In that analysis, patients who experienced IRAEs had statistically significant improvements in PFS (5.7 vs 2.0 months; HR 0.41; 95% CI 0.3-0.57; p < .001).
“PFS (5.7 vs 2.0 months (HR 0.41; 95% CI 0.3–0.57; p < .001))”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [34]
In that analysis, patients who experienced IRAEs had statistically significant improvements in OS (17.8 vs 4.0 months; HR 0.33; 95% CI 0.23-0.47; p < .001).
“OS (17.8 vs 4.0 months (HR 0.33; 95% CI 0.23–0.47; p < .001))”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [34]
In another large retrospective analysis of 195 NSCLC patients treated with nivolumab, 43.6% developed IRAEs.
“Of the included patients, 43.6% developed IRAEs with the most commonly involved sites being endocrine, gastrointestinal and dermatologic (unspecified percentages).”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [34]
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- Authors
- Ricciuti, B., Genova, C., De Giglio, A., Bassanelli, M., Dal Bello, M. G., Metro, G., Brambilla, M., Baglivo, S., Grossi, F., & Chiari, R.
- Affiliations
- Azienda Ospedaliera di Perugia (IT)
- Ospedale Policlinico San Martino (IT)
- Corresponding author
- Ricciuti, Biagio
- ORCID
- Venue
- Journal of Cancer Research and Clinical Oncology
- Published
- 2018-12-01
- Volume
- 145
- Issue
- 2
- Pages
- 479-485
- ISSN
- 0084-5353 (ISSN-L)
- 0171-5216
- 1432-1335
- PMC
- PMC11810236
- OpenAlex
- W2903486314
- Cited by
- 345
- References
- 11
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 57 · 2023: 39 · 2022: 56 · 2021: 75 · 2020: 59 · 2019: 24
- FWCI
- 14.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Cancer Research and Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- immune-related adverse events, nivolumab, non-small cell lung cancer, immune checkpoint inhibitors, survival, progression-free survival, overall survival, predictive biomarkers, immune-related pneumonitis, immune-related colitis, immune-related endocrinopathy, immune-related dermatitis, platinum-pretreated patients, long-term outcomes, landmark analysis, prognostic factors
- MeSH terms
- Antineoplastic Agents, Immunological, Nivolumab, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Female, Follow-Up Studies, Humans, Immunotherapy, Lung Neoplasms, Male, Middle Aged, Prognosis, Prospective Studies, Retrospective Studies, Survival Rate
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