CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Immune profiling of pancreatic cancer for radiotherapy with immunotherapy and targeted therapy: Biomarker analysis of a randomized phase 2 trial.
Immune profiling of pancreatic cancer for radiotherapy with immunotherapy and targeted therapy: Biomarker analysis of a randomized phase 2 trial.
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若进一步与 MEK 抑制剂靶向治疗联合，PD-L1、TILs 和突变 KRAS 可能成为一种生物标志物，用于指导胰腺癌放疗和免疫治疗方案的临床实践。
免疫治疗单药在胰腺癌中的生存获益有限，而以免疫治疗为核心的联合疗法作用仍有争议。因此，需要开发生物标志物，以精准选择胰腺癌免疫多模式治疗方案。
本研究是开放标签、随机、II期试验的二次分析，纳入术后局部复发胰腺癌患者。符合条件且携带KRAS突变、PD-L1免疫组化阳性的患者被随机分配接受立体定向体部放疗联合帕博利珠单抗和曲美替尼（SBRT+K+M），或SBRT联合吉西他滨（SBRT+G）。每组内进一步按PD-L1阳性/TIL（肿瘤浸润淋巴细胞）阴性和PD-L1阳性/TIL阳性分组。
共纳入170例患者，随机分配至SBRT+K+M组（n=85）或SBRT+G组（n=85）。既往研究已报告SBRT+K+M组患者结局改善。本次二次分析中，接受SBRT+K+M的PD-L1阳性/TIL阳性患者中位总生存期（OS）为17.2个月（95% CI 14.6–19.8），PD-L1阳性/TIL阴性患者为12.7个月（95% CI 10.8–14.6；HR 0.62，95% CI 0.39–0.97，p=0.036）。SBRT+G组中，PD-L1阳性/TIL阴性患者中位OS为13.1个月（95% CI 10.9–15.3），PD-L1阳性/TIL阳性患者为12.7个月（95% CI 9.2–16.2；HR 0.97，95% CI 0.62–1.52，p=0.896）。SBRT+K+M组中，PD-L1阳性/TIL阴性患者有16例（30.8%）、PD-L1阳性/TIL阳性患者有10例（30.3%）发生3或4级不良事件；SBRT+G组相应人数分别为9例（16.7%）和8例（25.8%）。
若联合MEK抑制剂作为靶向治疗，PD-L1、TIL和KRAS突变可能成为指导胰腺癌放疗及免疫治疗方案临床应用的生物标志物。
Immunotherapy alone offered limited survival benefits in pancreatic cancer, while the role of immunotherapy-centric combined therapy remains controversial. Therefore, it is required to develop biomarkers to precisely deliver immunotherapy-based multimodality for pancreatic cancer.
This is a secondary analysis of an open label, randomized, phase 2 trial, whereas patients with locally recurrent pancreatic cancer after surgery were enrolled. Eligible patients with mutant KRAS and positive immunohistochemical staining of PD-L1 were randomly assigned to receive stereotactic body radiation therapy (SBRT) plus pembrolizumab and trametinib (SBRT + K + M) or SBRT and gemcitabine (SBRT + G). Meanwhile, patients were classified into PD-L1+/tumor infiltrating lymphocytes [TIL(s)]- and PD-L1+/TIL + group for each arm.
A total of 170 patients were enrolled and randomly assigned to receive SBRT + K + M (n = 85) or SBRT + G (n = 85). The improved outcomes have been reported in patients with SBRT + K + M in the previous study. In this secondary analysis, the median overall survival (OS) was 17.2 months (95% CI 14.6-19.8 months) in patients with PD-L1+/TIL + and 12.7 months (95% CI 10.8-14.6 months) in patients with PD-L1+/TIL- (HR 0.62, 95% CI 0.39-0.97, p = 0.036) receiving SBRT + K + M. In SBRT + G group, the median OS was 13.1 months (95% CI 10.9-15.3 months) in patients with PD-L1+/TIL- and 12.7 months (95% CI 9.2-16.2 months) in patients with PD-L1+/TIL+ (HR 0.97, 95% CI 0.62-1.52, p = 0.896). Grade 3 or 4 adverse events were found in 16 patients (30.8%) and 10 patients (30.3%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + K + M group respectively; whereas 9 (16.7%) and 8 patients (25.8%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + G group.
PD-L1, TILs and mutant KRAS may be a biomarker to guide clinical practice of radiotherapy and immunotherapy-based regimens in pancreatic cancer if further combined with MEK inhibitors as targeted therapy.
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