Shaya Justin, Kato Shumei, Adashek Jacob J, Patel Hitendra, Fanta Paul T, Botta Gregory P, Sicklick Jason K, Kurzrock Razelle
Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
NPJ Genom Med. 2023 Jan 20;8(1):1. doi: 10.1038/s41525-022-00346-5.
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.
尽管取得了进展，但胰腺癌患者的2年生存率仍然很低。我们对18例（晚期/转移性胰腺癌）患者（来自分子肿瘤委员会）采用了一种生物标志物驱动的联合治疗/单病例研究策略。每位患者使用的靶向药物数量为2.5种（中位数）（范围为1 - 4种）；一线治疗（n = 5）；二线治疗（n = 13）。比较患者（高匹配度与低匹配度）（匹配分数≥50%与<50%；反映与靶向药物匹配的改变数量除以致病改变数量），生存期显著更长（风险比[HR] 0.24（95%置信区间[CI]，0.078 - 0.76，P = 0.016））；临床获益率（CBR）（疾病稳定≥6个月/部分/完全缓解）呈上升趋势（45.5%对0.0%，P = 0.10）；无进展生存期，HR，95% CI，0.36（0.12 - 1.10）（p = 0.075）。一线治疗与≥二线治疗相比，CBR更高（80.0%对7.7%，P = 0.008）。未发生3 - 4级毒性反应。最长的缓解者通过联合靶向MEK和CDK4/6改变（无化疗）实现了部分缓解（17.5个月）。因此，基因组匹配的靶向药物联合治疗在这些晚期胰腺癌中具有活性。有必要进行更大规模的前瞻性试验。
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