Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Kaiyang Fifth Road, Guangzhou, 510555, People's Republic of China.
Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 510060, People's Republic of China.
Cancer Immunol Immunother. 2024 Sep 5;73(11):220. doi: 10.1007/s00262-024-03796-1.
The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.
ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.
A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.
This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.
抗 PD-L1 抗体度伐利尤单抗已被批准用于一线治疗晚期胆管癌（ABC）。迄今为止，尚无疗效预测生物标志物。
回顾性纳入接受吉西他滨为基础的化疗加或不加度伐利尤单抗的 ABC 患者，并从病历中检索其基线临床病理指标。计算并分析总生存期（OS）和无进展生存期（PFS）。使用酶联免疫吸附试验试剂盒检测 48 例患者的外周生物标志物水平。对 27 例有肿瘤组织的患者进行靶向下一代测序，以描绘基因组改变。
2020 年 1 月至 2022 年 12 月期间，共纳入符合条件的 186 例 ABC 患者，其中 93 例患者接受化疗加度伐利尤单抗，其余患者仅接受化疗。与单纯化疗相比，度伐利尤单抗联合化疗显著改善了 PFS（6.77 个月比 4.99 个月；风险比 0.65 [95%CI 0.48-0.88]；P=0.005），但未改善 OS（14.29 个月比 13.24 个月；风险比 0.91 [95%CI 0.62-1.32]；P=0.608）。接受化疗加和不加度伐利尤单抗的患者的客观缓解率（ORR）分别为 19.1%和 7.8%。在接受度伐利尤单抗治疗的患者中，治疗前 sPD-L1、CSF1R 和 OPG 被确定为显著的预后预测因子。对化疗加度伐利尤单抗有反应的患者中富集了 ADGRB3 和 RNF43 突变，与生存改善相关。
这项回顾性真实世界研究证实了度伐利尤单抗联合化疗在治疗初治 ABC 患者中的临床获益。外周 sPD-L1 和 CSF1R 是这种治疗策略有前途的预后生物标志物。ADGRB3 或 RNF43 突变的存在可以改善免疫治疗结果的分层，但需要进一步研究以探索潜在机制。
