Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non-small cell lung cancer

Abstract

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.

An increased relative eosinophil count as a predictive dynamic biomarker in non‐small cell lung cancer patients treated with immune checkpoint inhibitors

“…Therefore, a long‐term follow‐up in a large prospective study is needed to validate the present results. We demonstrated the importance of pretreatment eosinophil counts and early mortality factors in ICI monotherapy for advanced or metastatic NSCLC 12,21 . The same population was examined as that in our previous study.…”

Pretreatment eosinophil counts as a predictive biomarker in non‐small cell lung cancer patients treated with immune checkpoint inhibitors

“…Furthermore, multicenter studies are needed due to the small number of cases. We reported early mortality factors in ICI monotherapy for advanced or metastatic NSCLC 24 . The same population was used in the present study and our previous research 24 .…”

“…According to previous studies, the baseline median values of neutrophil and lymphocyte counts were selected as cutoff values 24 . The baseline median values of CRP and Alb levels were also selected as cutoff values 24 . NLR <5 and tumor size <5 cm were selected as cutoff values following previous studies 25,26 .…”

The Palliative Prognostic (PaP) Score without Clinical Evaluation Predicts Early Mortality among Advanced NSCLC Patients Treated with Immunotherapy

“…The resulting score showed an AUC of 0.76 (95% CI: 0.70–0.81) for 90-day mortality, but no 30-day mortality analysis was performed. Another observational study explored the factors associated with 60-day mortality among 166 metastatic NSCLC treated with ICI single-agents [ 24 ]. Interestingly, laboratory findings (albumin, neutrophils, lymphocytes, C-reactive protein) failed to be independently associated with early death.…”