Abstract:

Objective　To observe the clinical effects of different programmed cell death protein receptor-1 (PD-1) inhibitors in the treatment of gastrointestinal tumors and their influences on the long-term survival in patients. Methods　This was a prospective randomized controlled study. A total of 125 patients with gastric cancer admitted to the First People's Hospital of Shangqiu City from October 2020 to January 22 were selected as the study subjects. The patients were divided into group A [63 patients, 32 males and 31 females, aged (60.44±5.23) years] and group B [62 patients, 32 males and 30 females, aged (61.24±5.18) years] by the random number table method. Both groups received standard chemotherapy. Group A was treated with nivolumab in combination with chemotherapy, while group B was treated with pembrolizumab in combination with chemotherapy. The short-term treatment effects of the two groups were compared, and the long-term survival of the two groups were compared through a one-year follow-up. t test and χ² test were used. Results　After treatment, the rate of complete remission [11.11% (7/63)] and partial remission [39.68% (25/63)] in group A were higher than those in group B [1.61% (1/62) and 22.58% (14/62)], and the rate of disease progression [3.17% (2/63)] was lower than that in group B [14.52% (9/62)], with statistically significant differences (χ²=4.706, 4.258, and 5.008; all P<0.05). After 8 weeks of treatment, the tumor growth rate (TGR) [(35.45±10.37)%] in group A was lower than that in group B [(40.33±10.59)%], the time to treatment failure (TTF) [(3.46±1.33) months] was longer than that in group B [(2.72±1.47) months], and the incidence of tumor hyperprogression (HPD) [19.05% (12/63)] was lower than that in group B [38.71% (24/62)], with statistically significant differences (t=2.603 and 2.952, χ²=5.891; all P<0.05). During follow-up, there was no statistically significant difference in the incidence of adverse reactions between the two groups (χ²=0.080, P>0.05). The median progression-free survival (PFS) [(12.47±3.44) months] and the median overall survival (OS) [(15.66±5.25) months] in group A were longer than those in group B [(10.35±3.62) months and (13.36±5.17) months], with statistically significant differences (t=3.357 and 2.468, both P<0.05). Conclusions　Nivolumab and pembrolizumab both can be used as adjunctive standard chemotherapy for gastric cancer patients. But compared with pembrolizumab, the drug toxicity of nivolumab is weaker, which can effectively increase the patients' clinical benefits, and also has a positive role in reducing the risk of HPD and prolonging their life cycle.

Key words:

Gastrointestinal tumors, Programmed cell death protein receptor-1 inhibitors, Tumor hyperprogression, Short-term efficacy,  , Survival

摘要：

目的　观察不同程序性细胞死亡蛋白受体-1（programmed cell death protein receptor-1，PD-1）抑制剂治疗胃肠道肿瘤的临床效果及对患者远期生存情况的影响。方法　本文为前瞻性随机对照试验。选取2020年10月至2022年1月期间商丘市第一人民医院收治的125例胃癌患者为研究对象，采用随机数字表法将患者分为A组［63例，男32例、女31例，年龄（60.44±5.23）岁］、B组［62例，男32例、女30例，年龄（61.24±5.18）岁］，两组患者均接受标准化疗。A组采用纳武利尤单抗配合化疗，B组采用帕博利珠单抗配合化疗。比较两组患者近期治疗效果，并通过开展为期1年的随访比较两组远期生存情况。采用t检验、χ²检验。结果　治疗后，A组患者疾病完全缓解率［11.11%（7/63）］、部分缓解率［39.68%（25/63）］均高于B组［1.61%（1/62）、22.58%（14/62）］，疾病进展率［3.17%（2/63）］低于B组［14.52%（9/62）］，差异均有统计学意义（χ²=4.706、4.258、5.008，均P<0.05）；A组治疗8周后的肿瘤生长率（TGR）［（35.45±10.37）%］低于B组［（40.33±10.59）%］，至治疗失败时间（TTF）［（3.46±1.33）个月］长于B组［（2.72±1.47）个月］，肿瘤超进展（HPD）发生率［19.05%（12/63）］低于B组［38.71%（24/62）］，差异均有统计学意义（t=2.603、2.952，χ²=5.891；均P<0.05）。随访期间，两组患者不良反应总发生率比较，差异无统计学意义（χ²=0.080，P>0.05）。A组患者中位无进展生存期（PFS）［（12.47±3.44）个月］、中位总生存期（OS）［（15.66±5.25）个月］均长于B组［（10.35±3.62）个月、（13.36±5.17）个月］，差异均有统计学意义（t=3.357、2.468，均P<0.05）。结论　纳武利尤单抗以及帕博利珠单抗均可辅助用于胃癌患者的标准化疗，但相比之下，纳武利尤单抗的药物毒性更弱，可有效增加患者临床获益，对降低肿瘤HPD风险并延长患者生存周期具有积极作用。

关键词:

胃肠道肿瘤, 程序性细胞死亡蛋白受体-1抑制剂, 肿瘤超进展, 近期疗效, 生存情况