Evaluation of the association between predictive factors and the development of immune-related adverse events and prognostic factors for chemoimmunotherapy in patients with non-small cell lung cancer: A multicenter retrospective study.

INTRODUCTION: Chemoimmunotherapy is widely used as the first-line management of advanced non-small cell lung cancer (NSCLC) in clinical settings. However, predictive factors associated with the development of immune-related adverse events (irAEs) and prognostic factors for NSCLC patients undergoing chemoimmunotherapy remains largely unexplored. Therefore, in this study, we aimed to evaluate predictive factors for irAE development and prognostic factors associated with chemoimmunotherapy in NSCLC patients. METHODS: This study enrolled 199 patients with advanced and recurrent NSCLC who underwent chemoimmunotherapy across eight institutions in Nagano prefecture from December 2018 to January 2023. We examined predictive factors associated with irAE development and prognostic factors associated with overall survival (OS). RESULTS: Among the patients, 106 experienced irAEs, while 93 patients did not. A total of 44 (22.1%) patients developed multiple irAEs. High serum albumin levels (Alb >3.5 g/dL) emerged as an independent predictive factor associated with irAE development in logistic regression analysis (odds ratio; 2.35, 95% confidence interval 1.27-4.34, p = 0.007). Furthermore, the development of multiple irAEs (p = 0.016), lower lactate dehydrogenase level (<223 U/L, p = 0.002), and decreased neutrophil-to-lymphocyte ratio (<3, p = 0.049) were identified as independent favorable prognostic factors associated with OS in multivariate Cox hazard analyses. CONCLUSION: The study results suggest that high serum Alb is a predictive factor for irAE development and that the presence of multiple irAEs is a favorable prognostic indicator for NSCLC patients undergoing chemoimmunotherapy.

Unfavorable response to capmatinib for MET exon14 skipping after first-line osimertinib in a patient with EGFR-mutated lung adenocarcinoma: A case report and literature review.

MET exon14 skipping mutations (METex14s) are rarely reported as a potential resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). The efficacy of targeted therapy against METex14s emerging after osimertinib resistance is uncertain. Herein, we report a case of EGFR-mutated metastatic lung adenocarcinoma in which METex14 was detected in a re-biopsy upon first-line osimertinib resistance. The patient received capmatinib monotherapy as third-line therapy, which was ineffective, followed by an exceptional response to salvage therapy with afatinib. This report highlights the heterogeneity of EGFR-TKI resistance and that targeting rare resistance mechanisms remains challenging.

Prognostic Value of the Geriatric Nutritional Risk Index in Previously Untreated Patients with Advanced Non-Small Cell Lung Cancer Treated with a Combination Therapy of Anti-PD-1/-PD-L1 Antibodies and Platinum-Based Chemotherapy: A Multicenter Retrospective Study.

INTRODUCTION: Combination therapy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies and platinum-based chemotherapy has been widely used as a first-line treatment for patients with unresectable advanced non-small cell lung cancer (NSCLC) in clinical settings; however, prognostic biomarkers associated with survival outcomes have not been sufficiently investigated. METHODS: We enrolled 147 previously untreated patients with advanced NSCLC who were treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy at eight institutions in Nagano Prefecture between December 2018 and April 2023. We evaluated the prognostic value of the geriatric nutritional risk index (GNRI), a systemic inflammatory nutritional biomarker calculated from body weight and serum albumin level, for patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy. RESULTS: The cutoff value of the GNRI was set at 92. The high GNRI and low GNRI groups included 88 and 59 patients, respectively. The median follow-up period was 15.9 months. The overall survival (OS) in the high GNRI group was significantly longer than that in the low GNRI group (27.9 vs. 15.6 months, p = 0.015). Multivariate analysis revealed that a high GNRI was an independently favorable prognostic predictor for OS (hazard ratio, 1.73; 95% confidence interval, 1.06-2.86; p = 0.031). CONCLUSION: The present study demonstrates that the GNRI is a useful prognostic predictor in patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy in clinical settings.

A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency.

Pembrolizumab is an anti-programmed cell death protein-1 antibody that is mainly used for the treatment of non-small cell lung cancer (NSCLC). Immune-related adverse events can be caused by immune checkpoint inhibitors; however, few case reports evaluate the prognosis of patients with NSCLC with late-onset immune-related adverse events. In this case, a 63-year-old man with stage IVA lung adenocarcinoma received pembrolizumab as first-line therapy and achieved a complete response. The patient developed hypothyroidism and skin toxicity owing to pembrolizumab over the course of treatment; however, the patient continued with pembrolizumab. The patient discontinued pembrolizumab after 20 cycles owing to appetite loss from 14 months after the initiation of pembrolizumab. Two months later, the symptoms worsened and the patient was taken to hospital by an ambulance owing to movement difficulty. The patient was diagnosed with acute adrenal insufficiency by endocrinological examinations. The condition of the patient improved after hydrocortisone treatment. Sixteen months have passed without the readministration of pembrolizumab and no recurrence of lung adenocarcinoma has been observed. Late-onset, severe, and diverse immune-related adverse events may be a favorable prognostic factor associated with survival.

Gefitinib Treatment Was Unsuccessful for Central Diabetes Insipidus Due to Pituitary Metastasis of Lung Adenocarcinoma.

We herein report a rare case of advanced lung adenocarcinoma with central diabetes insipidus due to pituitary metastasis. Although treatment with gefitinib was dramatically effective, the symptoms of diabetes insipidus did not improve. Radiotherapy for pituitary metastasis was effective to control diabetes insipidus; however, we could not cease the administration of 1-deamino-8-D-arginine vasopressin (DDAVP). It is important for physicians to positively consider radiotherapy for pituitary metastases even if favorable tumor control is achieved with chemotherapy when diabetes insipidus becomes clinically overt. Furthermore, continuous DDAVP administration may be needed to treat central diabetes insipidus.