Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Cancer Immunol Immunother. 2024 Jun 4;73(8):144. doi: 10.1007/s00262-024-03721-6.
The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial.
We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis.
Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029).
PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.
在低程序性死亡配体 1（PD-L1）表达的晚期胃或胃食管交界处（G/GEJ）腺癌患者中，一线程序性死亡-1（PD-1）抑制剂联合化疗的有益效果存在争议。
我们对 2017 年 10 月至 2022 年 5 月期间接受 PD-1 抑制剂联合化疗一线治疗的 G/GEJ 腺癌患者进行了回顾性分析。主要结局是客观缓解率（ORR）和无进展生存期（PFS）。使用 SPSS 软件 V27.0 进行数据分析。
在 345 名入组患者中，290 名有可测量的病变。总体 ORR 为 59.3%。PD-L1 状态在 171 名患者中可用，其中 67.8%被认为是低 PD-L1 表达水平（联合阳性评分（CPS）<5）。PD-L1 CPS<5 的患者反应率较低（51.1%比 70.8%，P=0.024），PFS 更差（P=0.009）。在 PD-L1 低表达队列中，非弥漫型、GEJ 癌、同步转移、远处淋巴结转移、肝转移、非腹膜转移和 HER2 阳性的患者对 PD-1 抑制剂联合化疗的反应率更高（P<0.05）。腹膜转移（P=0.028）和弥漫型（P=0.046）是 PD-L1 CPS<5 亚组多变量分析中无进展生存期不良的独立预测因素。在 PD-L1 低表达亚组中评估与总生存期（OS）的相关性时，发现腹膜转移是死亡风险增加的唯一独立预后因素（风险比：2.31，95%CI 1.09-4.90；P=0.029）。
PD-L1 CPS≥5 与 G/GEJ 癌症患者接受 PD-1 抑制剂联合化疗治疗的反应改善和 PFS 延长显著相关。低 PD-L1 表达人群中的特定亚组，如非弥漫型肿瘤且无腹膜转移的患者，也可能从免疫治疗联合化疗中获益。
