Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Oncology and Hemato-oncology Department, University of Milan, Italy.
Oncologist. 2020 Sep;25(9):803-809. doi: 10.1634/theoncologist.2020-0014. Epub 2020 May 20.
Few real-world series on the efficacy and safety of anti-programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)-based therapy are available in molecularly unselected patients with poor performance status (PS) and specific types of advanced cancers, because such populations are typically excluded from clinical trials due to poor life expectancy and risk of toxicity.
This multicenter retrospective case series included patients with microsatellite instability (MSI)-high metastatic cancers with Eastern Cooperative Oncology Group (ECOG) PS of 2 or 3 not related to comorbidities receiving anti-PD-1 with or without anti-CTLA-4 therapy after failure of at least one prior treatment line.
We included 27 patients with six diverse tumor types: colorectal (n = 18), gastric (n = 5), biliary tract, pancreatic, small bowel, and endometrial cancers (n = 1 each). Baseline ECOG PS was 2 (74%) or 3 (26%). Overall response rate was 33%, with six partial and three complete responses. Median time to response was 3.1, months and median duration of response was 16.9 months. Median progression-free survival was 3.4 months (95% CI: 2.3 to not evaluable), and 18-month overall survival was 50.8% (95% confidence interval, 32.7-78.8). Baseline variables were not associated with survival outcomes. ECOG PS 1 was reached by 52% of patients in a median time of 6 weeks, and ECOG PS 0 was reached by 30% of patients in a median time of 10 weeks.
In a high proportion of patients with MSI-high cancers and poor performance status related to end-stage disease, salvage immunotherapy can induce potentially long-lasting "Lazarus responses". Immunotherapy decisions near the end-of-life should be carefully integrated with predictive biomarkers and with palliative care measures in the real-world setting.
In this retrospective cohort study of 27 pretreated patients with microsatellite instability (MSI)-high cancers and Eastern Cooperative Oncology Group performance status of 2 or 3 not related to comorbidities, PD-1/PD-L1-based therapy induced a RECIST response in 33% of patients, with a median duration of 16.9 months, and an improvement of performance status in 52% of patients. MSI-high status can be used in clinical practice as a tumor-agnostic predictive biomarker to select critically ill patients with end-stage cancers for salvage immunotherapy.
在分子上未选择的、身体状况不佳（PS）和特定类型晚期癌症的患者中，很少有关于抗程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）的疗效和安全性的真实世界系列研究，因为由于预期寿命短和毒性风险，此类人群通常被排除在临床试验之外。
这项多中心回顾性病例系列研究纳入了 ECOG PS 为 2 或 3（与合并症无关）的微卫星不稳定（MSI）高转移性癌症患者，这些患者在至少接受过一线治疗后失败，接受了抗 PD-1 联合或不联合抗 CTLA-4 治疗。
我们纳入了 27 名患者，其中有 6 种不同的肿瘤类型：结直肠癌（n=18）、胃癌（n=5）、胆道癌、胰腺癌、小肠癌和子宫内膜癌（n=1 种）。基线 ECOG PS 为 2（74%）或 3（26%）。总体缓解率为 33%，有 6 例部分缓解和 3 例完全缓解。中位反应时间为 3.1 个月，中位缓解持续时间为 16.9 个月。中位无进展生存期为 3.4 个月（95%CI：2.3 至不可评估），18 个月总生存率为 50.8%（95%置信区间，32.7-78.8）。基线变量与生存结果无关。中位时间为 6 周时，52%的患者达到 ECOG PS 1，中位时间为 10 周时，30%的患者达到 ECOG PS 0。
在很大比例的 MSI 高癌症和与终末期疾病相关的身体状况不佳的患者中，挽救性免疫治疗可以诱导潜在的长期“拉撒路反应”。在终末期，免疫治疗决策应与预测生物标志物和姑息治疗措施仔细结合，这在真实世界环境中至关重要。
在这项针对 27 名接受过治疗的 MSI 高癌症和 ECOG PS 为 2 或 3（与合并症无关）的患者的回顾性队列研究中，PD-1/PD-L1 治疗在 33%的患者中诱导了 RECIST 缓解，中位缓解持续时间为 16.9 个月，并且 52%的患者身体状况得到改善。MSI 高状态可在临床实践中用作肿瘤非特异性预测生物标志物，以选择处于终末期的危急癌症患者进行挽救性免疫治疗。
