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一名携带意义未明变异的肺癌患者对达拉非尼联合曲美替尼治疗反应增强:病例报告

Enhanced response to dabrafenib plus trametinib in a patient with lung cancer harboring an variant of unknown significance: a case report.

作者信息

D'Argento Ettore, Vitale Antonio, Russo Jacopo, Minucci Angelo, Cancellieri Alessandra, Stefani Alessio, Monaca Federico, Horn Guido, Occhipinti Denis, Troisi Paola, Scala Alessandro, Polidori Sara, D'Argento Francesco, Di Salvatore Mariantonietta, Bria Emilio, Tortora Giampaolo

机构信息

Comprehensive Cancer Center, Medical Oncology Department, Fondazione Policlinico, Universitario Agostino Gemelli IRCCS, Rome, Italy.

Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.

出版信息

Front Oncol. 2025 Jul 15;15:1600457. doi: 10.3389/fonc.2025.1600457. eCollection 2025.

Abstract

BACKGROUND

Literature evidence reports that (ring finger protein 43) gene mutations could serve as predictive biomarkers of response to certain anti-cancer therapies. To delve deeper into the specific role of mutations in lung cancer and their relevance to therapy response, we provide the first report of marked efficacy of the dabrafenib and trametinib therapeutic combination in a patient with microsatellite-stable (MSS) non-small-cell lung cancer (NSCLC) with and mutations.

CASE DESCRIPTION

An 85-year-old patient was diagnosed with NSCLC with the presence of MSS, and mutations. The patient started the combination treatment with dabrafenib and trametinib, soon reporting an overall clinical benefit. A contrast-enhanced cranio-thorax-abdomen CT scan performed after 1 month of therapy reported a sharp reduction in lung cancer and hilo-mediastinal lymphadenomegaly; the central colliquation of the left adrenal metastasis was also reported. After 9 months of therapy, the cranio-thorax-abdomen CT scan with contrast medium confirmed the reduction of the adenocarcinoma, with residual scarring component; the right adrenal lesion was not visible, and the contralateral lesion was stable. At the last follow-up (February 2024), the global clinical condition of the patient was good; she was autonomous, and oxygen therapy was not necessary.

CONCLUSIONS

Our clinical case represents the first report of marked efficacy of the dabrafenib-trametinib combination reported in an 85-year-old patient diagnosed with NSCLC with the presence of MSS, and mutations. This supports the hypothesis on the relevance of mutations in predicting the clinical benefit of targeted therapies and in modulating the anti-tumor activity of anti-BRAF therapies, suggesting that mutations represent a promising biomarker that warrants further validation for its potential to help prioritize therapy combinations in selected lung cancer patients.

摘要

背景

文献证据表明,(无名指蛋白43)基因突变可作为某些抗癌疗法反应的预测生物标志物。为了更深入地研究基因突变在肺癌中的具体作用及其与治疗反应的相关性,我们首次报告了达拉非尼和曲美替尼联合治疗对一名患有微卫星稳定(MSS)非小细胞肺癌(NSCLC)且存在和基因突变患者的显著疗效。

病例描述

一名85岁患者被诊断为患有MSS、和基因突变的NSCLC。患者开始接受达拉非尼和曲美替尼联合治疗,很快就报告了总体临床获益。治疗1个月后进行的增强颅胸腹部CT扫描报告显示肺癌和肺门纵隔淋巴结肿大明显减轻;还报告了左肾上腺转移灶的中央液化。治疗9个月后,增强颅胸腹部CT扫描证实腺癌缩小,有残留瘢痕成分;右侧肾上腺病变不可见,对侧病变稳定。在最后一次随访(2024年2月)时,患者整体临床状况良好;她生活自理,无需吸氧治疗。

结论

我们的临床病例首次报告了达拉非尼 - 曲美替尼联合治疗对一名85岁、被诊断为患有MSS、和基因突变的NSCLC患者具有显著疗效。这支持了关于基因突变在预测靶向治疗临床获益和调节抗BRAF治疗抗肿瘤活性方面相关性的假设,表明基因突变是一种有前景的生物标志物,其有助于在特定肺癌患者中优先选择治疗方案的潜力值得进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/477e/12303935/3afa47b40cb5/fonc-15-1600457-g001.jpg

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