METHODS: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn\'t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.
CONCLUSIONS: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
方法:我们介绍了1例多发性转移性PDAC,IHC错配修复有效,但HER-2IHC弱阳性诊断,一线nab-紫杉醇联合吉西他滨和PD-1抑制剂治疗后肿瘤没有消退。RC48(HER2-抗体-药物偶联物)的新型联合治疗PRaG3.0,放射治疗,PD-1抑制剂,然后应用粒细胞-巨噬细胞集落刺激因子和白细胞介素-2作为二线治疗,患者确认部分缓解良好,无进展生存期为6.5个月,总生存期为14.2个月.她在任何时候都没有出现任何2级或以上的治疗相关不良事件。在包含放疗的PRaG3.0治疗的前两个激活周期中,外周CD8Temra和CD4Temra的百分比增加,但在不包含放疗的维持周期中降低至基线。
结论:PRaG3.0可能是HER2阳性转移性PDAC患者的一种新策略,这些患者以前的一线方法甚至PD-1免疫治疗均失败,但在前瞻性试验中需要更多数据。