Sugumar Kavin, Alabd Andrew, Alabd Andre, Hue Jonathan J, Lyons Josh, Fields Sherri, Wainberg Zev, Zheng Lei, Coogle Brianna, Kasi Anup, Grewal Nicholas, Kindler Hedy L, Starr Jason, Sama Ashwin R, Winter Jordan M
Department of Surgery, University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA.
Department of Medicine, Cooper University Healthcare, Camden, NJ 08103, USA.
Oncotarget. 2025 Jun 10;16:427-442. doi: 10.18632/oncotarget.28739.
Immunotherapy has emerged as a standard treatment option for multiple solid tumors. However, most patients with pancreatic cancer (PC) do not derive a significant benefit. Identification and analyses of exceptional responders could eventually offer hints as to why PC is resistant to immunotherapy.
Oncologists from cancer centers in the United States were contacted to identify patients with PC who responded to immunotherapy. Exceptional responders were defined as those having either partial (PR) or complete response (CR) based on Response Evaluation Criteria in Solid Tumors, or biochemical response (CA 19-9 levels) after starting immunotherapy. Patients receiving concurrent chemotherapy were excluded.
14 patients met inclusion criteria. Immunotherapy drugs included checkpoint inhibitors and macrophage inhibitors. Eight patients (42%) were MSI (microsatellite instability)-high. Radiologically, 82% had PR. Four patients (28%) had marked reduction in CA 19-9. The median progression-free survival was 12 months from the start of immunotherapy. Median survival was not reached. The 1- and 2-year survival probabilities were 80%, 70% respectively.
Majority of clinical trials evaluating immunotherapy in PC have yielded disappointing response rates compared to other solid tumors. Our case series adds to published data from early-phase trials supporting the promise of immunotherapy in some patients with PC.
免疫疗法已成为多种实体瘤的标准治疗选择。然而，大多数胰腺癌（PC）患者并未从中获得显著益处。识别和分析特殊反应者最终可能会提示PC对免疫疗法耐药的原因。
联系了美国癌症中心的肿瘤学家，以识别对免疫疗法有反应的PC患者。根据实体瘤疗效评价标准，特殊反应者定义为部分缓解（PR）或完全缓解（CR）的患者，或开始免疫治疗后的生化反应（CA 19-9水平）。排除接受同步化疗的患者。
14例患者符合纳入标准。免疫治疗药物包括检查点抑制剂和巨噬细胞抑制剂。8例患者（42%）为微卫星高度不稳定（MSI）。影像学上，82%的患者有PR。4例患者（28%）的CA 19-9显著降低。从免疫治疗开始计算，无进展生存期的中位数为12个月。总生存期未达到中位数。1年和2年生存率分别为80%、70%。
与其他实体瘤相比，大多数评估PC免疫疗法的临床试验反应率令人失望。我们的病例系列补充了早期试验的已发表数据，支持免疫疗法对部分PC患者的前景。
