下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Long-term survival after immunotherapy and targeted therapy without chemotherapy in an elderly patient with HER2-positive gastroesophageal junction cancer: A case report.
HER2(3+)和PD-L1(<5%)免疫组化染色为阳性。
一名74岁男性接受胸腔镜联合根治性胃切除术,术后病理诊断为食管及贲门癌,pT3N1M0、pStage IIB。HER2免疫组化染色阳性(3+),PD-L1阳性率<5%。患者发生严重血小板减少(血小板计数<30×10^9/L),且报告期间未恢复,因此未接受辅助化疗。术后10.7个月,患者发生腹膜、肝、肺和骨等多器官转移。一线接受2个周期曲妥珠单抗联合帕博利珠单抗(200 mg)后,发生2级免疫相关肌炎、2级心肌炎及1级肝炎,遂停用帕博利珠单抗。此后曲妥珠单抗单药治疗,同时开始过继性CIK细胞输注。初次免疫治疗8个月后发现单发脑转移,患者接受射波刀放射外科治疗。二线仍采用过继性CIK细胞免疫治疗联合曲妥珠单抗。报告时,患者脑部和肝脏达到完全缓解,髂骨病灶部分缓解;随访已达36.6个月,明显长于晚期胃食管结合部癌患者的中位生存时间。作者认为,HER2靶向治疗以及帕博利珠单抗或CIK过继细胞输注免疫治疗,延长了这位HER2阳性、多发转移的老年胃食管结合部癌患者的总生存期。
A 74-yr-old man underwent thoracic laparoscopy combined with radical gastrectomy, and the postoperative pathological diagnosis was esophageal and gastric cardia cancer pT3N1M0, pStage IIB. Immunohistochemical staining for HER2 (3+) and PD-L1 (<5%) was positive. Adjuvant chemotherapy was not performed because the patient developed severe thrombocytopenia (platelet counts <30 × 10 9 /L), which was never cured throughout the reporting period. At 10.7 months post-surgery, he suffered metastases in multiple organs, including the peritoneum, liver, lung, and bone. Following two cycles of first-line trastuzumab and pembrolizumab (200 mg), he developed immune-related myositis (G2), myocarditis (G2), and hepatitis (G1). Therefore, pembrolizumab was discontinued. Trastuzumab was administered as a monotherapy; meanwhile, adoptive cytokine-induced killer (CIK) cell infusions were initiated. Eight months after the initial immunotherapy, a solitary brain metastasis was detected, and the patient underwent CyberKnife radiosurgery. For second-line therapy, adoptive CIK cell immunotherapy plus trastuzumab was still used. At the time of reporting, the patient had achieved a complete response (CR) in the brain and liver and a partial response (PR) in the ilium, and he had been followed-up for 36.6 months, much longer than the median survival time for patients with advanced GEJ cancer. We suggest that HER2-targeted therapy and immunotherapy with pembrolizumab or CIK adoptive cell infusions prolonged the overall survival of an elderly patient with HER2-positive GEJ cancer with multiple metastases.
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