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免疫疗法治疗晚期或转移性胃癌患者治疗前血红蛋白(Hb)的预后价值

The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy.

作者信息

Gou Miaomiao, Zhang Yong, Liu Tiee, Qu Tongtong, Si Haiyan, Wang Zhikuan, Yan Huan, Qian Niansong, Dai Guanghai

机构信息

Medical Oncology Department, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.

Medical Oncology Department, The Second Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.

出版信息

Front Oncol. 2021 Jun 15;11:655716. doi: 10.3389/fonc.2021.655716. eCollection 2021.

Abstract

BACKGROUND

Biomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC.

METHODS

We retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level.

RESULTS

We included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001).

CONCLUSIONS

Our study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.

摘要

背景

诸如当前的程序性死亡受体配体1(PD-L1)表达和肿瘤突变负荷(TMB)等生物标志物已被提出作为预测晚期胃癌(AGC)和转移性胃癌(MGC)患者免疫治疗结果的一种方式。我们的研究旨在调查AGC和MGC患者治疗前血红蛋白(Hb)水平与免疫治疗生存率之间是否存在关联。

方法

我们回顾性分析了在中国人民解放军总医院肿瘤科接受PD-1抑制剂治疗的AGC或MGC患者。采用倾向评分匹配法(PSM)(1:1)来平衡潜在的基线混杂因素。分析不同Hb水平(正常Hb组和降低Hb组)之间的无进展生存期(PFS)和总生存期(OS)。还分析了客观缓解率(ORR)、疾病控制率(DCR)。进一步进行单因素分析和多因素分析以验证Hb水平的预后价值。

结果

本研究纳入了137例接受PD-1抑制剂(包括帕博利珠单抗、纳武利尤单抗、信迪利单抗、特瑞普利单抗)治疗的AGC和MGC患者。经过PSM匹配后,两组的基线特征无显著差异。在匹配队列中,正常Hb水平组的中位PFS为7.8个月,降低Hb组为4.3个月(风险比[HR] 95%置信区间[CI] 0.5[0.31, 0.81],P = 0.004)。正常Hb水平组的OS为14.4个月,而降低Hb水平组为8.2个月(HR 95% CI 0.59[0.37, 0.94],P = 0.024)。正常Hb组的ORR为40.7%,DCR为83.0%,而降低Hb组的ORR为25.5%,DCR为85.1%。两组之间的ORR和DCR无显著差异(P = 0.127,P = 0.779)。单因素分析和多因素分析表明,Hb水平是PFS的唯一独立预测因素,基线Hb水平是影响OS的显著预后因素。仅当患者Hb水平正常时,抗PD-1单药治疗或联合化疗在PFS(10.3个月对2.8个月,HR 95% CI 0.37[0.15, 0.95],P = 0.031)和OS(15个月对5.7个月,HR 95% CI 0.21[0.08, 0.58],P = 0.001)方面优于抗PD-1加抗血管生成治疗。

结论

我们的研究表明,治疗前Hb水平是AGC和MGC患者免疫治疗中PFS和OS方面的独立预后生物标志物。对GC患者进行贫血纠正作为免疫治疗将是提高生存率的一种策略。需要更多数据来进一步影响这一发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe8e/8239234/c005f321cc05/fonc-11-655716-g001.jpg

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