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ABSTRACT Introduction Methods Results Conclusion First‐line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR‐tyrosine kinase inhibitor (TKI) is often performed after first‐line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR‐TKI rechallenge after first‐line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR‐TKI rechallenge with another TKI.This multicenter prospective observational study enrolled patients with EGFR‐mutated NSCLC who received first‐line osimertinib and another EGFR‐TKI as second‐ or third‐line treatment between September 2018 and August 2020.Fifty‐three patients received rechallenge with another EGFR‐TKI in the second‐line (n = 38, 71.7%) or third‐line (n = 15, 28.3%) setting. The primary reason for first‐line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR‐TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real‐world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR‐TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis.EGFR‐TKI rechallenge with another TKI is well tolerated in patients with EGFR‐mutated NSCLC. Thus, it may be a useful treatment option after first‐line osimertinib failure, especially after osimertinib discontinuation due to toxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Primary tracheal adenoid cystic carcinoma (TACC) is a rare low-grade lung cancer of bronchial gland origin. Surgery is the first choice of treatment; however, in cases of recurrence or inoperability, a combination of radiation and chemotherapy is administered as a multimodality treatment. Interventional bronchoscopy is also used as a multidisciplinary treatment; however, its impact on long-term prognosis has not been thoroughly investigated. Case Presentation: Eight patients diagnosed with TACC and treated at Shinshu University Hospital between December 2000 and August 2023 were analyzed retrospectively. We investigated the duration of intervention and overall survival (OS) in 3 patients with recurrence who underwent interventional bronchoscopy in combination with chemotherapy and evaluated whether interventional bronchoscopy prolonged the survival. The initial treatment for the 3 patients was surgery in 1 patient and chemoradiotherapy in 2. In all patients, raised lesions were observed in the trachea at the time of recurrence. The duration of interventional bronchoscopy, the time from recurrence of the first-line treatment to death, and OS, which was defined time from induction of the first-line treatment to death, were 69.3/70.7/112.5 months, 179.2/196.1/220.4 months, and 15.4/66.3/104.4 months, respectively. Conclusion: Long-term survival benefits may be obtained with concomitant interventional bronchoscopy in combination with chemotherapy in patients with locally recurrent TACC. [ABSTRACT FROM AUTHOR]

An 80‐year‐old woman with no lung disease or autoimmune disease presented with a productive cough, lasting for 2 months. Chest computed tomography revealed a transbronchial dispersal shadow in the left upper lobe, and sputum culture showed Gram‐positive rods. The identified causative organism was Rothia aeria, and thus, she was treated with oral trimethoprim/sulfamethoxazole (TMP–SMX). Eleven days after initiating TMP–SMX treatment, she returned with a complaint of dyspnoea. While the sputum culture revealed normal flora, the patient's condition was diagnosed as bronchitis during R. aeria pneumonia treatment; therefore, she was hospitalized. Five days after admission, her laboratory findings revealed agranulocytosis, caused by an adverse event of TMP–SMX. Her neutrophil count increased after discontinuing TMP–SMX treatment. Bronchitis was alleviated with intravenous antibiotic administration, and she was discharged on Day 8. We report a rare case of R. aeria pneumonia in an immunocompetent patient. [ABSTRACT FROM AUTHOR]

Background: In the LUX‐Lung 3 and LUX‐Lung 6 trials, afatinib improved overall survival in previously untreated patients with EGFR 19del mutated non‐small cell lung cancer (NSCLC) compared to chemotherapy. The appropriate management of adverse events and dose reduction of afatinib are important for EGFR‐positive NSCLC patients. We conducted a retrospective and observational study of patients treated with first‐line afatinib for EGFR‐positive NSCLC in Nagano prefecture, Japan, focusing on efficacy and toxicities. Methods: We retrospectively collected the medical records of NSCLC patients initially treated with afatinib between May 2014 and March 2018. Results: A total of 62 patients with a median age of 67 years and a median body surface area (BSA) of 1.57 m2 were included. The overall response rate was 87.7% and median progression‐free survival (PFS) was 15.7 months. The median PFS was similar between standard initial dose (40 mg) and reduced initial doses (30 and 20 mg) (15.7 vs. 14.2 months; P = 0.978). The frequency of dose reduction and the discontinuation rate in the 40 mg daily dose group was higher in patients with BSA < 1.58 m2 (100%) compared to BSA ≥ 1.58 m2 (68.2%) (P = 0.014). The frequency of diarrhea was higher in patients with BSA < 1.58 m2 (93.5%) compared to BSA ≥ 1.58 m2 (71.0%) (P = 0.02). Conclusion: In real‐world clinical practice, first‐line afatinib was well managed and was equally as effective as in previous clinical trials of EGFR‐positive NSCLC. BSA is considered a predictive marker for appropriate afatinib dose reduction. [ABSTRACT FROM AUTHOR]

A 71-year-old man was referred to our hospital for treatment of non-small-cell lung cancer (adenocarcinoma of the lungs, with multiple bone metastases, cT1bN0M1b, harboring an EGFR mutation [exon 19 deletion]). Gefitinib was administered as daily oral doses of 250 mg. After 18 days, gefitinib was discontinued because of hepatotoxicity (Grade 3). Forty days later, afatinib was administered as daily oral doses of 40 mg. Within 1 year, the primary tumor and bone metastases achieved a partial response without hepatotoxicity. We suggest that afatinib is an effective and well-tolerated treatment option for patients with hepatotoxicity under gefitinib treatment.