RESUMO
Introduction: Sotorasib is a crucial therapeutic agent for patients with non-small cell lung cancer (NSCLC) harboring the KRAS p.G12C mutation. Despite its efficacy, the relationship between blood sotorasib concentrations and side effects remains largely unexplored. Methods: This study enrolled five patients with KRAS p.G12C-positive NSCLC treated with sotorasib (LUMAKRAS® Tablets, Amgen, Japan) between July 2022 and February 2023 at Asahikawa Medical University Hospital. Blood sotorasib levels were monitored, and their association with adverse events was examined, with no adjustments made to drug dosages based on these levels. Results: Variable blood sotorasib levels were observed among the participants. Notably, one patient developed interstitial pneumonitis, although a definitive attribution to sotorasib was uncertain due to prior pembrolizumab treatment. The study revealed no consistent association between blood sotorasib levels and adverse events or therapeutic outcomes, with some patients experiencing severe side effects at higher concentrations, while others did not. Conclusion: Preliminary findings suggested that monitoring blood sotorasib levels may aid in anticipating adverse events in this small cohort. However, future studies with larger sample sizes and extended follow-up periods are required to validate these initial observations. Such studies could potentially offer insights into personalized dosing strategies, thereby mitigating adverse effects and enhance patient care for individuals with KRAS p.G12C-positive NSCLC.
RESUMO
Background: Tyrosine kinase inhibitors (TKIs) significantly improve clinical outcomes in patients with non-small cell lung cancer due to anaplastic lymphoma kinase (ALK) gene rearrangement. However, the rate of relapse with TKIs is high owing to the development of resistance mutations during treatment. Repeated biopsies during disease progression are crucial for elucidating the molecular mechanisms underlying the development of resistance to ALK inhibitors. Analysis of cell-free DNA (cfDNA) obtained from plasma is a novel approach for tumor genotyping. Methods: In this mixed prospective and retrospective observational cohort study, we investigated the clinical feasibility of continuous quantitative monitoring of ALK-acquired mutations in plasma obtained from patients with ALK+ non-small cell lung cancer by using a highly sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay. We enrolled nine patients, including three treatment-naïve patients recently diagnosed with ALK+ non-small cell lung cancer via tissue biopsy and expected to receive ALK TKIs and six patients already receiving ALK TKIs. Plasma samples were collected from these patients every 3 months. cfDNA was extracted from 66 samples during the study period, and 10 ALK mutations were simultaneously evaluated. Results: The numbers of samples showing the G1202R, C1156Y, G1269A, F1174L, T1151ins, and I1171T mutations were 32, 16, 5, 4, 1, and 1, respectively. The L1196M, L1152R, V1180L, and S1206Y mutations were not detected. Correlation analyses between progression-free survival and the time from treatment initiation (or treatment modification) to the detection of resistance mutations revealed that although resistance mutations may occur before a drug change becomes necessary, there is a duration during which the disease does not progress. Conclusions: Our findings suggest that real-time quantitative monitoring of ALK resistance mutations during the response period could provide a time course of changes while acquiring resistance mutations. This information would be beneficial for designing an appropriate treatment strategy.
RESUMO
A patient with late phase of COVID-19 pneumonia presented peripheral cystic features on chest computed tomography, which were spontaneously resolved with no antibiotic therapy or surgery. Physicians should pay attention to follow up the late phase of COVID-19 pneumonia for better understanding its progression and clinical course.
