尽管取得了进展，但胰腺癌2年存活率仍然令人沮丧。我们在18名患有晚期/转移性胰腺癌患者中参考了分子肿瘤委员会的生物标志物驱动的组合/N-of-one策略。每位患者均接受了2.5个（中值）靶向剂的治疗（范围为1-4个），其中5位患者进行第一线治疗，13位患者进行第二线治疗。通过比较高程度匹配和低程度匹配的患者(匹配分数≥50%和<50%, 反映匹配到的突变数量占致病突变总数的比例)，发现高度匹配的患者存活时间显著较长(HR0.24, 95% CI, 0.078-0.76, P=0.016)，临床受益率(稳定疾病时间≥6个月/部分或完全缓解的比例)趋向更高(45.5% vs 0.0%, P=0.10)，无进展生存期是HR, 95% CI, 0.36 (0.12-1.10) (p=0.075)。进行第一线治疗的患者与进行≥二线治疗的患者相比，临床受益率更高(80.0% vs 7.7%, P=0.008)。没有发生3-4级的毒性反应。最长持续缓解期为17.5个月，通过联合作用MEK和CDK4/6突变(无需化疗)实现了部分缓解。因此，基因组匹配的靶向药物组合对这些晚期胰腺癌患者疗效显著，更大的前瞻性试验是必要的。©2023作者。

Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/patient = 2.5 (median) (range, 1-4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078-0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12-1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = 0.008). No grade 3-4 toxicities occurred. The longest responder achieved partial remission (17.5 months) by co-targeting MEK and CDK4/6 alterations (chemotherapy-free). Therefore, genomically matched targeted agent combinations were active in these advanced pancreatic cancers. Larger prospective trials are warranted.© 2023. The Author(s).