Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non–Small-Cell Lung Cancer
Open accessAbstract
IMPORTANCE: Immune-related adverse events (irAEs) have been associated with the efficacy of PD-1 (programmed cell death protein 1) inhibitors in patients with melanoma, but whether such an association exists for non-small-cell lung cancer (NSCLC) has remained unknown. OBJECTIVE: To evaluate the relation of irAEs to nivolumab efficacy in NSCLC. DESIGN, SETTING, AND PARTICIPANTS: In this study based on landmark and multivariable analyses, a total of 134 patients with advanced or recurrent NSCLC who were treated with nivolumab in the second-line setting or later between December 2015 and August 2016 were identified from a review of medical records from multiple institutions, including a university hospital and community hospitals. Data were updated as of December 31, 2016. EXPOSURES: The absence or presence of any irAE before the landmark date. MAIN OUTCOMES AND MEASURES: Kaplan-Meier curves of progression-free survival (PFS) according to the development of irAEs in 6-week landmark analysis were evaluated with the log-rank test as a preplanned primary objective. Overall survival (OS) was similarly evaluated. Multivariable analysis of both PFS and OS was performed with Cox proportional hazard regression models. RESULTS: In a cohort of 134 patients (median [range] age, 68 [33-85] years; 90 men [67%], 44 women [33%]), irAEs were observed in 69 of the 134 study patients (51%), including 12 patients (9%) with such events of grade 3 or 4, and 24 patients (18%) requiring systemic corticosteroid therapy. In 6-week landmark analysis, median PFS was 9.2 months (95% CI, 4.4 to not reached [NR]) and 4.8 months (95% CI, 3.0 to 7.5) (P = .04) whereas median OS was NR (95% CI, 12.3 to NR) and 11.1 months (95% CI, 9.6 to NR) (P = .01) for patients with or without irAEs, respectively. Multivariable analysis also revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.525 (95% CI, 0.287 to 0.937; P = .03) for PFS and 0.282 (95% CI, 0.101 to 0.667; P = .003) for OS. CONCLUSIONS AND RELEVANCE: Development of irAEs was associated with survival outcome of nivolumab treatment in patients with advanced or recurrent NSCLC. Further studies are needed to confirm our findings.
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Occurrence of immune-related adverse events (irAEs) is associated with better survival, as suggested by others.
“as suggested by others if there was an occurrence of irAEs [58,59,60].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [58]
Patients who develop immune-related adverse events are more sensitive to ICI treatment.
“This is also consistent with the report that patients who develop immune-related adverse events are more sensitive to ICI treatment.48”
From The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti–Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC (2019) · cites this paper as [48]
Patients with irAEs experience survival benefits from PD-1 blockers.
“Patients with irAEs experience survival benefits from PD‑1 blocker(35).”
From Clinical impact of inflammatory and nutrition index based on metabolic tumor activity in non‑small cell lung cancer treated with immunotherapy. (2024) · cites this paper as [35]
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- Authors
- Haratani, K., Hayashi, H., Chiba, Y., Kudo, K., Yonesaka, K., Kato, R., Kaneda, H., Hasegawa, Y., Tanaka, K., Takeda, M., & Nakagawa, K.
- Affiliations
- Kindai University (JP)
- Kindai University Hospital (JP)
- Osaka Minami Medical Center (JP)
- Kishiwada City Hospital (JP)
- Izumi City General Hospital (JP)
- Corresponding author
- Hayashi, Hidetoshi
- ORCID
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2018-03-01
- Volume
- 4
- Issue
- 3
- Pages
- 374
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC6583041
- OpenAlex
- W2759963646
- Cited by
- 1,003
- References
- 16
- Citations by year
- 2026: 56 · 2025: 87 · 2024: 117 · 2023: 98 · 2022: 124 · 2021: 174 · 2020: 152 · 2019: 135 · 2018: 56 · 2017: 2 · 2016: 1 · 2013: 1
- FWCI
- 41.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK
- 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, PD-1 inhibitors, immune checkpoint inhibitors, progression-free survival, overall survival, second-line therapy, immune-related pneumonitis, immune-related colitis, corticosteroid therapy, treatment efficacy, immune-related toxicity, landmark analysis, multivariable analysis, prognostic factors
- MeSH terms
- Nivolumab, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immune System Diseases, Immunotherapy, Lung Neoplasms, Male, Middle Aged, Prognosis, Retrospective Studies, Biomarkers, Tumor, Cohort Studies, Treatment Outcome, Chemotherapy, Adjuvant, Biomarkers, Pharmacological, Drug-Related Side Effects and Adverse Reactions
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