Assistance Publique - Hôpitaux de Paris, Georges Pompidou European Hospital, Department of Hepato-Gastroenterology and Gastrointestinal Oncology, Department of Oncology, Université Paris Cité, SIRIC CARPEM, Paris, France; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale contre le cancer, Paris, France.
Assistance Publique - Hôpitaux de Paris, Georges Pompidou European Hospital, Department of Hepato-Gastroenterology and Gastrointestinal Oncology, Department of Oncology, Université Paris Cité, SIRIC CARPEM, Paris, France.
Eur J Cancer. 2023 Jul;188:90-97. doi: 10.1016/j.ejca.2023.04.012. Epub 2023 Apr 23.
Immune checkpoint inhibitors (ICIs) improve oncological outcomes in patients with microsatellite instability-high (MSI) or mismatch repair-deficient (dMMR) advanced solid tumours. Nevertheless, based on limited published data, the outcome of patients with MSI/dMMR pancreatic ductal adenocarcinoma (PDAC) seems poorer when compared to other malignancies. This multi-institutional analysis sought to assess the efficacy and tolerability of ICIs in a large real-world cohort of patients with MSI/dMMR PDAC.
We retrospectively collected data from patients with MSI/dMMR advanced PDAC treated with ICIs in 16 centers. Progression-free survival and overall survival were calculated from the start of treatment, and we report objective response and disease control rates according to RECIST V1.1.
Thirty-one MSI/dMMR advanced PDAC patients were identified. Twenty-five patients received single-agent anti-PD-1 antibodies, three patients received the combination of nivolumab and ipilimumab and three patients received immunotherapy in combination with chemotherapy. Among 31 evaluable patients, 15 (48.4%) had an objective response (three complete responses and 12 partial responses), and six (19.4%) had stable disease. With a median follow-up of 18 months, the median progression-free survival (PFS) was 26.7 months and the median overall survival (OS) was not reached. Disease control rates (DCRs) among patients with only one line of prior therapy (N = 17) was 76.5%. Grade 3-4 treatment-related adverse events were not observed.
This retrospective analysis suggests that ICIs are effective and well tolerated in patients with MSI/dMMR advanced PDAC. Hence, our work supports the use of PD-1 inhibition in this group of patients with high unmet medical need.
免疫检查点抑制剂（ICI）可改善微卫星不稳定高（MSI）或错配修复缺陷（dMMR）晚期实体瘤患者的肿瘤学结局。然而，基于有限的已发表数据，与其他恶性肿瘤相比，MSI/dMMR 胰腺导管腺癌（PDAC）患者的结局似乎较差。这项多机构分析旨在评估 ICI 在 MSI/dMMR 晚期 PDAC 患者的大型真实世界队列中的疗效和耐受性。
我们回顾性地收集了在 16 个中心接受 ICI 治疗的 MSI/dMMR 晚期 PDAC 患者的数据。从治疗开始计算无进展生存期和总生存期，并根据 RECIST V1.1 报告客观缓解率和疾病控制率。
确定了 31 例 MSI/dMMR 晚期 PDAC 患者。25 例患者接受了单药抗 PD-1 抗体治疗，3 例患者接受了纳武单抗和伊匹单抗联合治疗，3 例患者接受了免疫治疗联合化疗。在 31 例可评估患者中，15 例（48.4%）有客观缓解（3 例完全缓解，12 例部分缓解），6 例（19.4%）有稳定疾病。中位随访 18 个月时，中位无进展生存期（PFS）为 26.7 个月，中位总生存期（OS）未达到。仅接受一线既往治疗的患者（N=17）的疾病控制率（DCR）为 76.5%。未观察到 3-4 级治疗相关不良事件。
这项回顾性分析表明，ICI 对 MSI/dMMR 晚期 PDAC 患者有效且耐受性良好。因此，我们的工作支持在这群有高度未满足医疗需求的患者中使用 PD-1 抑制。
