Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

In stroke patients, upper extremity deep vein thrombosis (UEDVT) is uncommon compared with lower extremity. Unlike the blood stasis in lower extremity, UEDVT has been developed by secondary cause. We reported a case of stroke patient with repeated UEDVT, presenting superficial venous congestion, who was finally diagnosed with pulmonary adenocarcinoma. The cause of stroke was non-bacterial thromboembolism formed at the mitral valve. Our case shows that unexpected UEDVT should be closely evaluated for higher coagulable status such as a malignancy.

Background/Aims: The prognostic value of a comprehensive geriatric assessment (CGA) for the management of older small cell lung cancer (SCLC) patients remains to be established. Methods: A retrospective cohort enrolled 21 SCLC patients over 65 years from March 2018 to 2019 at the Yonsei Cancer Center. The CGA included the following instruments: frailty, body mass index, sarcopenia (circumference of arm and calf, Timed Up and Go test, grip strength), comorbidity, polypharmacy, activities of daily living (ADL), Instrumental ADL, nutrition, depression, and cognitive function. The correlations of oncological and geriatric variables with overall survival (OS) were determined. The log-rank test with Cox model and Kaplan-Meier method were used for the analysis. Results: The median age was 75 years (range, 67 to 85). All patients had the Eastern Cooperative Oncology Group performance status 0–2. The median survival was 9.93 months (range, 1.53 to 36.30). Among CGA parameters, ADL and nutritional status had significant differences in OS in univariate analysis. In multivariate analysis, only nutritional status was independently associated with survival (hazard ratio, 0.17; 95% confidence interval, 0.05 to 0.57). Median OS for low nutritional status was 5.63 months and the normal nutrition group was 15.5 months (p = 0.004). Conclusions Pre-treatment nutritional status measured by CGA appears to be a predictor of OS in older SCLC patients. However, for further generalization of the implication of CGA in SCLC, a larger scale study with prospective design is strongly needed.

Purpose: This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents. Materials and Methods: Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed. Results: The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively. Conclusion Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

Lazertinib is an oral, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that forms an irreversible covalent bond to the Cys797 residue in the ATP-binding site of the EGFR kinase domain and exhibits a high selectivity for sensitizing and T790M EGFR mutations. In January 2021, it was first approved for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) patients with EGFR T790M who had previously received EGFR TKI therapy based on LASER201, a phase I/II trial. At a recommended dose of 240 mg, lazertinib achieved an encouraging anti-tumor activity in both extra- and intracranial lesions. With a high half-maximal inhibitory concentration for EGFR wildtype tumors, it is anticipated to pose a lower risk of skin and cardiac adverse events compared to osimertinib. Lazertinib is currently being investigated as a monotherapy in first-line treatment and in combination with amivantamab under various settings. In this review, we systematically summarize the preclinical and clinical data of lazertinib and discuss future perspectives on the treatment of EGFR-mutant NSCLC.

Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. Methods The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023.

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer’s disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer’s disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

In acute stroke, emboli are mostly composed of thrombi from artery, cardiac chamber, valve and vein. Non-thrombotic emboli are sometimes difficult to identify the origin. According to the increased number of cancer patients, now 10% of stroke patients have a cancer. However, the potential mechanisms of stroke in patients with cancer are various. We presented a case of serious acute arterial occlusion with a tumor embolus, which was revealed by histopathologic analysis of retrieved emboli during mechanical thrombectomy.