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Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non-small cell lung
Eiji Takeuchi1, Kensuke Kondo2, Yoshio Okano3
1Department of Clinical Investigation, National Hospital Organization Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi, Kochi, 780-8507, Japan. eijitake1964@icloud.com.
Purpose:
Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer.
Patients And Methods:
We retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment.
Results:
A total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophil-to-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes < 22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin < 3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio [OR], 10.3; p = 0.008), ECOG PS score ≥ 2 (OR, 8.0; p = 0.007), and a smoking history (OR, 0.1; p = 0.03) were significant risk factors for early death.
Conclusion:
Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.
Insights
Immune checkpoint inhibitors (ICI) can cause early death in lung cancer patients. Liver metastases, poor performance status (ECOG PS ≥ 2), and non-smoking history are key risk factors for early mortality.
Area of Science:
- Oncology
- Immunotherapy
- Lung Cancer Research
Background:
- Immune checkpoint inhibitors (ICI) offer a promising treatment avenue for advanced or metastatic non-small cell lung cancer (NSCLC).
- However, a subset of patients experience hyperprogressive disease or early mortality following ICI monotherapy.
- Identifying factors associated with early death is crucial for optimizing treatment strategies and patient selection.
Purpose of the Study:
- To investigate the factors contributing to early mortality in patients with advanced or metastatic NSCLC treated with ICI monotherapy.
- To identify specific clinical and laboratory parameters predictive of death within 60 days of initiating ICI treatment.
Main Methods:
- A retrospective review of 166 patients with advanced or metastatic NSCLC treated with nivolumab, pembrolizumab, or atezolizumab monotherapy between March 2016 and August 2021.
- Early death was defined as mortality within 60 days of commencing ICI treatment.
- Statistical analyses, including univariate and multivariate logistic regression, were employed to identify significant risk factors.
Main Results:
- Of 166 patients, 21 (12.7%) experienced early death.
- Univariate analysis identified ECOG Performance Status (PS) ≥ 2, liver metastasis, larger tumor size (≥ 5 cm), specific neutrophil and lymphocyte counts, elevated serum neutrophil-to-lymphocyte ratio (sNLR), increased C-reactive protein (CRP), and low albumin as significant risk factors.
- Multivariate analysis confirmed liver metastasis (OR, 10.3), ECOG PS ≥ 2 (OR, 8.0), and a non-smoking history (OR, 0.1) as independent predictors of early mortality.
Conclusions:
- Liver metastases, an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2 or higher, and a non-smoking history are significant early mortality factors in patients receiving ICI monotherapy for advanced or metastatic NSCLC.
- These findings highlight the importance of assessing these factors for risk stratification and personalized treatment approaches in NSCLC patients undergoing immunotherapy.
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