克里唑蒂尼
医学
培美曲塞
肿瘤科
肺癌
内科学
卡铂
贝伐单抗
腺癌
癌症研究
作者
Zhaoting Meng,Cuicui Zhang,Ran Zuo,Fuyi Zhu,Yajie Wang,Re Mi,Meng Zhang,Peng Chen
标识
DOI:10.1097/cad.0000000000001291
摘要
Selpercatinib has been approved by most major regulatory bodies in 2020 and become the standard therapy for rearranged during transfection (RET)-rearranged nonsmall-cell lung cancer (NSCLC). Knowledge is limited regarding mechanisms of resistance to selpercatinib and effective treatment. One study identified MNNG HOS transforming (MET) amplification as intrinsic or secondary resistance mechanism from four patients, and three of them showed ~40% tumor reduction when treated with selpercatinib plus crizotinib. We report a 30-year-old female nonsmoker diagnosed in 2019 with stage IV lung adenocarcinoma harboring KIF5B-RET and a novel FOXD1-RET fusion. Frontline therapy consisted of bevacizumab combined with pemetrexed and carboplatin and achieved a progression-free survival (PFS) of 14 months with best response of stable disease. The patient then enrolled in the LIBRETTO-321 trial (NCT03157129) and started selpercatinib, which elicited a PFS of 9 months with best response of partial response. MNNG HOS transforming (MET) amplification was subsequently detected upon progression on selpercatinib, and the patient was placed on third-line treatment with selpercatinib plus crizotinib. However, her health deteriorated rapidly and died of cancer 4 months later. We provided additional evidence supporting MET amplification as an acquired mechanism of resistance to selective RET inhibition. In addition, the apparent lack of response to selpercatinib plus crizotinib in this case highlights the need for future cohort studies for examining the value of combining RET and MET inhibitors in treating RET-rearranged, MET-amplified NSCLC.
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