Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
J Immunother. 2023 Apr 1;46(3):111-119. doi: 10.1097/CJI.0000000000000458. Epub 2023 Feb 22.
Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.
免疫疗法联合化疗是目前 PD-L1 阳性胃癌的一线治疗选择。然而，对于老年或体弱的胃癌患者，最佳治疗策略仍然是未满足的医疗需求。先前的研究表明，PD-L1 表达、EB 病毒关联和微卫星高度不稳定（MSI-H）是胃癌免疫治疗的潜在预测生物标志物。在本研究中，我们通过对癌症基因组图谱胃腺癌队列的分析发现，与 70 岁以下的患者相比，70 岁以上的老年胃癌患者的 PD-L1 表达、肿瘤突变负担和 MSI-H 比例显著升高[≥70/＜70：MSI-H：26.8%/15.0%，P=0.003；肿瘤突变负担：6.7/5.1 Mut/Mb，P=0.0004；PD-L1 mRNA：5.6/3.9 每百万映射读数的计数，P=0.005]。在我们的真实世界研究中，分析了 416 例胃癌患者，结果相似（≥70/＜70：MSI-H：12.5%/6.6%，P=0.041；联合阳性评分≥1：38.1%/21.5%，P＜0.001）。我们还评估了 16 例接受免疫治疗的老年胃癌患者，结果显示客观缓解率为 43.8%，中位总生存期为 14.8 个月，中位无进展生存期为 7.0 个月。我们的研究表明，对于老年胃癌患者，免疫治疗可获得持久的临床缓解，值得进一步研究。
