Unexpected Cardiotoxicity in Patients With HER2-Mutant NSCLC Treated With Trastuzumab Deruxtecan: A Case Report.

Antibody-drug conjugates targeting receptor tyrosine-protein kinase erbB-2 (ERBB2, HER2) have emerged as promising targeted options for HER2-mutant NSCLC. Among antibody-drug conjugates targeting HER2, trastuzumab deruxtecan was found to have the most impressive efficacy and is a potential new standard of care. Drug-related interstitial lung disease remains a serious unpredictable identified risk for patients treated with trastuzumab deruxtecan, requiring careful monitoring and multidisciplinary management. We report the first two cases of drug-related cardiotoxicity with acute myocarditis that developed after the first trastuzumab deruxtecan cycle. Routine cardiovascular risk screening is advisable, with close collaboration between cardiology specialists and oncologists.

Real-World Utility of an Amplicon-Based Next-Generation Sequencing Liquid Biopsy for Broad Molecular Profiling in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: To assess the feasibility and utility of circulating tumor DNA (ctDNA) by amplicon-based next-generation sequencing (NGS) analysis in the daily clinical setting in a cohort of patients with advanced non-small-cell lung cancer (NSCLC), as an alternative approach to tissue molecular profiling. PATIENTS AND METHODS: In this single-center prospective study, treatment-naïve and previously treated patients with advanced NSCLC were enrolled. Clinical validation of ctDNA using amplicon-based NGS analysis (with a 36-gene panel) was performed against standard-of-care tissue molecular analysis in treatment-naïve patients. The feasibility, utility, and prognostic value of ctDNA as a dynamic marker of treatment efficacy was evaluated. Results of tissue molecular profile were blinded during ctDNA analysis. RESULTS: Of 214 patients with advanced NSCLC who were recruited, 156 were treatment-naïve patients and 58 were pretreated patients with unknown tissue molecular profile. ctDNA screening was successfully performed for 91% (n = 194) of all patients, and mutations were detected in 77% of these patients. Tissue molecular analysis was available for 111 patients (52%), and tissue somatic mutations were found for 78% (n = 87) of patients. For clinically relevant variants, concordance agreement between ctDNA and tumor tissue analysis was 95% among 94 treatment-naïve patients who had concurrent liquid and tumor biopsy molecular profiles. Sensitivity and specificity were 81% and 97%, respectively. Of the 103 patients with no tissue available, ctDNA detected potential actionable mutations in 17% of patients; of these, 10% received personalized treatment. ctDNA kinetics correlated with response rate and progression-free survival in 31 patients treated with first-line platinum-based chemotherapy. CONCLUSION: These real-world data from a prospective study endorse ctDNA molecular profile by amplicon-based NGS as an accurate and reliable tool to detect and monitor clinically relevant molecular alterations in patients with advanced NSCLC.