PDF(Pubmed)
Abstract：
Comprehensive genome profiling (CGP) is expected to widen the scope of cancer drug options by identifying the genes involved in carcinogenesis. However, a few patients can access recommended treatments following CGP. Herein, we report a case in which pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, was used as last-line therapy to treat a patient with advanced gastric cancer exhibiting FGFR2 genomic alterations, as determined by CGP testing. The patient (male, 52 years old) was diagnosed with advanced gastric cancer (cStage IV, cT4aN3M1 [LYM], por, HER2 0, microsatellite stable) and received docetaxel + cisplatin + S-1 (7 cycles), irinotecan + ramucirumab (11 cycles), and nivolumab (3 cycles), but experienced progressive disease (PD). Subsequently, FoundationOne Liquid CDx testing was conducted, revealing FGFR2 rearrangement and amplification; however, no clinical trials on genotype-matched therapies for FGFR2 alterations were available. After three cycles of TAS-102, the patient experienced PD and provided consent for the off-label use of pemigatinib. The Cancer Genomics Medical Committee of our hospital approved the self-funded treatment. The patient had markedly decreased CEA and CA19-9 levels after treatment initiation, but experienced PD after five courses. Over the treatment course, grade 1 hyperphosphatemia and onychomadesis were observed. To the best of our knowledge, this is the first reported case of pemigatinib therapy employed in a patient with advanced gastric cancer exhibiting FGFR2 gene alterations. This case could serve as a notable example of tumor-agnostic therapy to broaden treatment options for gastric cancer patients with rare genetic alterations.
摘要：
综合基因组分析（CGP）有望通过确定参与致癌作用的基因来扩大癌症药物选择的范围。然而,少数患者可以在CGP后获得推荐的治疗。在这里，我们报告了一个病例，其中pemigatinib，选择性成纤维细胞生长因子受体（FGFR）抑制剂，被用作最后一线治疗，以治疗表现出FGFR2基因组改变的晚期胃癌患者，由CGP测试确定。患者（男性，52岁)被诊断为晚期胃癌(cIV期，cT4aN3M1[LYM],波尔，HER20，微卫星稳定），并接受多西他赛+顺铂+S-1（7个周期），伊立替康+雷莫珠单抗（11个周期），和nivolumab（3个周期），但经历了进行性疾病（PD）。随后，进行了一次液体CDx测试,揭示FGFR2重排和扩增；然而，目前尚无针对FGFR2改变的基因型匹配疗法的临床试验.在TAS-102的三个周期后，患者经历了PD，并同意在标签外使用培米加替尼。我院肿瘤基因组学医学委员会批准自费治疗。患者在治疗开始后CEA和CA19-9水平明显下降，但经历了五门课程后的PD。在治疗过程中，观察到1级高磷血症和甲癣。据我们所知,这是报道的首例Pemigatinib治疗出现FGFR2基因改变的晚期胃癌患者.该病例可以作为肿瘤不可知疗法的一个值得注意的例子，以扩大具有罕见遗传改变的胃癌患者的治疗选择。
