Introduction The burden of melanoma is increasing globally. Despite the use of immunotherapy and targeted therapy, the prognosis of metastatic melanoma remains relatively poor. The integration of comprehensive molecular profiling can lead to the detection of actionable biomarkers and the expansion of treatment options, thereby prolonging cancer patient survival. Case Presentation We herein present the case of a female 54-year-old patient diagnosed with melanoma of the right knee, for which she underwent surgery. Patient showed progression of disease after 10 cycles of adjuvant nivolumab. Ipilimumab (1 mg/kg every 3 weeks) was added to the treatment regimen but no clinical improvement was observed. Molecular profiling was conducted based on patient tissue, and an ANXA2-NTRK3 fusion was detected in the tumor. This specific fusion has not been previously reported; however, it is in-frame and similar to other known oncogenic NTRK fusions. At the time of entrectinib initiation, the patient had clear disease progression on the right leg on standard of care immunotherapy. She was commenced on entrectinib 200 mg once daily for 2 weeks. Dose escalation was attempted, and treatment intensity was managed based on drug tolerability. Good treatment response was observed on laboratory and radiologic parameters. As of September 2023, i.e., 2.5 years after treatment initiation, patient disease continues to be controlled with entrectinib. Conclusion Profiling of advanced tumors is important to determine the presence of agnostic markers that can be targeted and ultimately improve the prognostic outcome of patients after the failure of standard of care.

中文翻译：

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Entrectinib 治疗 NTRK 融合阳性转移性黑色素瘤，PD-1 和 CTLA-4 联合抑制后进展：病例报告。

简介 全球黑色素瘤的负担正在增加。尽管使用免疫疗法和靶向治疗，转移性黑色素瘤的预后仍然相对较差。综合分子分析的整合可以检测可操作的生物标志物并扩大治疗选择，从而延长癌症患者的生存期。病例介绍 我们在此介绍一名 54 岁女性患者的病例，她被诊断患有右膝黑色素瘤，并接受了手术。10 个周期的纳武单抗辅助治疗后，患者出现疾病进展。治疗方案中添加了易普利姆玛（Ipilimumab，每 3 周 1 mg/kg），但没有观察到临床改善。根据患者组织进行分子分析，并在肿瘤中检测到 ANXA2-NTRK3 融合。这种特定的融合以前没有报道过；然而，它与其他已知的致癌 NTRK 融合符合框且相似。在开始恩曲替尼治疗时，患者在标准免疫治疗下右腿出现明显的疾病进展。她开始服用 entrectinib 200 mg，每日一次，持续两周。尝试增加剂量，并根据药物耐受性管理治疗强度。在实验室和放射学参数上观察到良好的治疗反应。截至 2023 年 9 月，即开始治疗后 2.5 年，患者疾病继续受到恩曲替尼的控制。结论 晚期肿瘤的分析对于确定可靶向的不可知标记物的存在非常重要，并最终改善标准护理失败后患者的预后结果。