Background: Clinically measurable factors affecting the progression-free survival (PFS) of patients receiving osimertinib as first-line therapy for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC)have not yet been established. Methods: We retrospectively reviewed the medical records of 61 patients treated with osimertinib as primary therapy for EGFR mutation-positive advanced NSCLC at Yokohama City University Medical Center between August 2018 and March 2022. Our objective was to identify the independent predictors of PFS. Results: The median age of participants was 74 years. Overall, 73.8% had good (0-1) Eastern Cooperative Oncology Group performance status (PS), and 98.4% had histology of adenocarcinoma. The EGFR mutation was exon19 deletion in 52.5% and exon21 L858R in 44.3% of patients. Programmed death-ligand 1 tumor proportion score >50% was observed in 21.3% and liver metastasis in 9.9% of patients. Median PFS was 19.5 months (95% confidence interval [CI]: 10.6-31.6), and overall survival was not reached. The objective response rate was 68.9%, and disease control rate was 93.4%. Multivariate analysis showed that poor PS (2-4) negatively impacted PFS (hazard ratio, 3.79; 95% CI: 1.46-9.87; p = 0.006). Median PFS in the good PS and poor PS groups was 20.4 months (95% CI: 12.4-not evaluable) and 7.2 months (95% CI: 7.2-19.5), respectively. Interstitial lung disease of all grades and grade 3 was observed as an adverse event in 6.6 and 4.9% of patients, respectively. Conclusion: Poor PS was associated with poor prognosis in patients with EGFR mutation-positive advanced NSCLC treated with osimertinib as first-line therapy.

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Background: Advanced non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. However, outcomes have gradually improved after the introduction of novel immunotherapies, including immune checkpoint inhibitors (ICIs). Although programmed death-ligand 1 (PD-L1) expression in tumor tissues is a known biomarker for guiding ICI treatment of NSCLC, challenges such as difficulty of liquid biopsy and heterogeneous results during treatment persist. This study evaluated the potential of miR200b as a surrogate biomarker for PD-L1 expression. Methods: We used the human lung cancer cell lines H226, H460, H520, A549, and H1975. miR200b expression in blood and bronchoscopy specimens of NSCLC patients was evaluated using reverse-transcription-quantitative PCR. Using flow cytometry, PD-L1 expression in vitro, as well as in tumor tissues, was evaluated after transfection with a mimic miR200b or siRNA. Results: miR200b expression negatively correlated with PD-L1 expression in all cell lines. The induction or knockdown of miR200b also altered PD-L1 expression in vitro. The patient group with a PD-L1 tumor proportion score ≥ 50% had significantly lower miR200b expression in the bronchoscopy specimens (P = 0.025) and serum-derived exosomes (P = 0.022) than that with PD-L1 tumor proportion score < 50%. Conclusions: miR200b can regulate PD-L1 expression in lung cancer cells, and miR200b expression in clinical specimens negatively correlated with PD-L1 expression. Thus, miR200b may be a useful surrogate biomarker for PD-L1 expression in lung cancer patients.

Background/Aim: Immune checkpoint inhibitors (ICIs) have an important role in lung cancer therapy. Although the programmed cell death protein-1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden are known prognostic factors, they are insufficient to predict clinical outcomes. This study was conducted to identify novel biomarkers for ICI treatment. Patients and Methods: We performed univariable and multivariable analyses of 110 patients with advanced non-small-cell lung cancer (NSCLC) who were treated with an ICI to identify novel biomarkers related to prognosis. We assessed their backgrounds, such as performance status (PS), PD-L1 TPS, smoking status, and peripheral white blood cell counts at baseline and on the day the second course of ICI administration. Results: In the multivariable analysis, PS, driver gene, immune-related adverse events, and post-treatment absolute neutrophil counts (post-ANCs) were significantly associated with progressionfree survival. Conclusion: A high level of post-ANCs was associated with poor outcome in ICI-treated NSCLC patients.Emergence of immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab, and atezolizumab, has led to a paradigm shift in the treatment of non-small-cell lung cancer (NSCLC). Although the combination of ICIs and cytotoxic agents has been recently adapted for first-line chemotherapy regardless of the programmed cell death protein-1 (PD-L1) tumor proportion score (TPS) (1), ICI monotherapy remains the standard therapy for NSCLC patients with PD-L1 high expression (2). The PD-L1 TPS and tumor mutational burden (TMB) are known major predictive markers for ICI (3-5). Among patients with ≥50% PD-L1 expression, the response rate to pembrolizumab monotherapy has been found to be 45.2%, whereas among patients with <1% PD-L1 expression, the response rate of pembrolizumab monotherapy was 7.8% (6). Although the PD-L1 TPS is an important biomarker for ICI, high expression of PD-L1 is not always observed in patients who are successfully treated with an ICI. In a certain number of patients with the risk of immune-related adverse events (irAEs), ICIs provide no clinical benefit. Thus, more effective and easily measurable biomarkers for ICI are needed for clinical use. Some biomarkers assessed in the peripheral blood of ICItreated patients have previously been reported. High lactate dehydrogenase (LDH) and high C-reactive protein (CRP) at baseline have been reported to be associated with poor outcome (7, 8). High neutrophil-lymphocyte ratio (NLR) (9, 10), high absolute lymphocyte counts (ALCs), high absolute eosinophil counts (AECs), and high absolute neutrophil counts (ANCs) prior to induction of ICI have been shown to be associated with progression-free survival (PFS) and overall survival (OS) in NSCLC patients (11). Clinical biomarkers, poor performance status (PS) (9, 12), appearance of any irAEs (13), and expression of driver gene mutation ( 14) have also been reported to be associated with poor prognosis in NSCLC patients.The aim of this study ...

A 58-year-old man was diagnosed with lung adenocarcinoma with a tumor proportion score of 10%. After six cycles of second-line chemotherapy with nivolumab, he achieved a complete response (CR) but developed uveitis and sensorineural hearing disorder, which were consistent with Vogt-Koyanagi-Harada (VKH)-like syndrome. Simultaneously, pituitary adrenocortical insufficiency was identified. Nivolumab discontinuation and systemic corticosteroid administration resolved these immune-related adverse events (irAEs). The patient has maintained a CR without any chemotherapy for approximately two years. We herein report a patient with a long-term progression-free survival despite chemotherapy discontinuation due to irAEs, including VKH-like syndrome, which were appropriately managed.