Miso Kim

Background: Central nervous system (CNS) involvement remains a major cause of mortality in patients with epidermal growth factor receptor (EGFR)‐mutated nonsmall cell lung cancer (NSCLC), particularly, after progression on EGFR tyrosine kinase inhibitors (TKIs). This pooled analysis evaluated the efficacy of lazertinib in patients with EGFR ‐mutated NSCLC and CNS involvement, using data from two Phase II trials. Patients and Methods: Patients with EGFR ‐mutated NSCLC and CNS involvement following prior EGFR TKI therapy enrolled in the KCSG‐LU20‐15 and KCSG‐LU21‐01 were included. Overall and intracranial objective response rate (ORR), disease control rate (DCR), and progression‐free survival (PFS) were assessed. Results: Seventy‐two patients were included. The median age was 63 years and 45 patients (62.5%) had leptomeningeal metastases (LM). T790M status was positive in 7 patients, negative in 44, and unknown in 21. Intracranial tumor responses were evaluable in 46 patients; the intracranial ORR was 50.0%, and the intracranial DCR was 97.8%. The median intracranial PFS was 15.2 months. Among 66 patients evaluable for systemic response, the overall ORR and DCR were 22.7% and 97.0%, respectively. The median PFS and overall survival were 10.6 and 17.8 months, respectively. Patients with LM experienced inferior OS and intracranial PFS compared with those without LM. No significant differences in clinical outcomes were observed according to T790M status. Conclusion: Lazertinib demonstrated meaningful CNS activity in patients with EGFR ‐mutated NSCLC and CNS involvement after prior EGFR TKI exposure, including those with LM. Notably, this activity was observed in a cohort with a low prevalence of confirmed T790M positivity.

Despite the immunomodulatory mechanism of immune checkpoint inhibitors (ICIs), systemic glucocorticoids are commonly used in advanced non–small cell lung cancer (NSCLC). Evidence regarding their effects on ICI outcomes is inconsistent, in part due to confounding by indication and immortal time bias. We conducted a multicenter target trial emulation to assess the association of glucocorticoid timing and dose with survival outcomes while addressing these biases. Patients with advanced NSCLC who initiated ICI therapy between 2015 and 2021 at four Korean tertiary hospitals were included. The primary endpoint was 2‐year overall survival (OS), with disease progression as a secondary endpoint. To minimize biases, outcomes were compared between concomitant glucocorticoid users and non‐users using time‐dependent propensity score matching. Among 1,815 eligible patients, 1,128 were matched. Hazard ratios (HRs) from the four institutions were pooled using a random‐effects meta‐analysis. Concomitant glucocorticoid use was associated with an increased risk of mortality (pooled aHR 1.36; 95% CI, 1.06–1.75). Early exposure within 90 days of ICI initiation was associated with poorer OS (aHR 1.49; 95% CI, 1.18–1.87), whereas later initiation showed no association. Dose‐stratified analyses showed that high‐dose exposure (> 1 mg/kg/day) was associated with reduced survival (aHR 1.61; 95% CI, 1.31–1.99), whereas low‐dose exposure was not associated with adverse outcomes. After accounting for confounding by indication and time‐related biases, concomitant systemic glucocorticoid use during ICI therapy was associated with less favorable survival outcomes. This association was more pronounced with early and high‐dose exposure, underscoring the clinical importance of glucocorticoid timing and dose.

Inflammatory myofibroblastic tumor (IMT) is a rare entity, primarily affecting young individuals, often involving the abdomen, pelvis, or lung. Approximately 50% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors a viable treatment. We report a case of a 40-year-old female with metastatic IMT harboring a CARS1-ALK fusion. Initial chemotherapy failed, but targeted therapy with alectinib through the KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study led to significant tumor regression and ongoing, durable clinical improvement of 19 months. This case highlights the importance of precision medicine and raises the reappraisal of targeted agents outside of approved indications for rare cancers with actionable genomic alterations.

The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells