CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study.
Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study.
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免疫检查点抑制剂（ICI）已经彻底改变了癌症的治疗格局。然而，最佳患者选择仍是一个未满足的需求。在这项观察性研究中，前瞻性招募了146名在巴塞罗那医院临床试验单位接受ICI治疗的转移性癌症候选患者。在不同时间点采集血样，计算基线LIPI评分，并调取ICI前存档组织以评估PD-L1、TIL（肿瘤浸润淋巴细胞）（TILs）和PD1 mRNA水平。肿瘤评估由中心依据RECIST 1.1标准进行审查。在适当情况下，采用单变量/多变量逻辑回归和Cox回归分析与总缓解率（ORR）、持久临床获益（DCB）、无进展生存期（PFS）和总生存期（OS）的关联。中位随访26.9个月时，中位PFS和OS分别为2.7个月和12.9个月。
缓解率为17.8%，缓解持续时间（DOR）为4.4个月。LIPI评分与PFS（p = 0.025）和OS（p < 0.001）独立相关。免疫治疗初治状态与更好的PFS独立相关（p = 0.005）。单变量分析中，最佳缓解时间（TTBR）和ORR（两者p < 0.001）与更好的OS相关。PFS和DOR与OS呈中度相关（两者p < 0.001）。PD-L1 10%截断值在ORR（单变量p = 0.011，多变量p = 0.028）和DCB（单变量p = 0.043）方面可识别较差/最佳缓解者。PD1 mRNA水平与完全缓解显著相关（p = 0.021）。
总之，在我们的前瞻性观察性泛癌研究中，基线LIPI评分、免疫治疗初治状态、癌症类型以及开始ICI前接受RT是与免疫治疗结局独立相关的最重要临床因素。较长的TTBR似乎与更好的生存相关，而PD1 mRNA和PD-L1蛋白水平可能是对ICI应答的肿瘤不可知预测因素，应进一步探索。
Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer.
However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1. 1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26. 9 months, median PFS and OS were 2. 7 and 12. 9 months. Response rates were 17. 8% with duration of response (DOR) of 4. 4 months. LIPI score was independently associated with PFS (p = 0.
025) and OS (p < 0. 001). Immunotherapy-naïve status was independently associated with better PFS (p = 0. 005). Time-to-best response (TTBR) and ORR (p < 0. 001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0. 001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0. 011, multivariate p = 0. 028) and DCB (univariate p = 0. 043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.
021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored.
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