Gemcitabine combined with apatinib and toripalimab in recurrent or metastatic nasopharyngeal carcinoma
Gemcitabine combined with apatinib and toripalimab in recurrent or metastatic nasopharyngeal carcinoma
复制标题
DOI：
10.1016/j.medj.2022.07.009
复制
发表时间：
2022-10-14
期刊：
影响因子：
17
通讯作者：
Chen, Ming-Yuan
中科院分区：
文献类型：
--
作者：
You, Rui;Zou, Xiong;Chen, Ming-Yuan
背景资料：吉西他滨（化疗）+阿帕替尼（抗血管内皮生长因子[VEGFR]）和托里帕利单抗（抗PD-1）（GAT）三联疗法在复发/转移性鼻咽癌（RM-NPC）中的作用尚不清楚。方法：2019年8月至2020年4月期间，41例RM-NPC患者入组，接受GAT长达6个周期，随后接受阿帕替尼和托里帕利单抗。主要终点是安全性。次要终点包括客观缓解率（ORR）和无进展生存期（PFS）。结果：截至2022年4月1日，41例患者中有23例发生了治疗相关的3级或4级不良事件（AE）（56.1%，95%置信区间[CI] 41%-70.1%）。9例（9/41，21.9%）患者观察到G3-4鼻咽坏死。坏死的高风险因素包括重复放疗和距离最后一次放疗间隔不到12个月。ORR为90.2%（95% CI：76.9%-97.2%）。中位PFS为25.8个月（95%CI：未达到（NR）-NR），24个月PFS率为50.7%（95%CI：34.0%-67.4%）。肿瘤中MAS相关GPR家族成员F（MRGPRF）的高表达与GAT治疗的PFS较差相关，其特征在于高上皮间充质转化特征。结论：GAT治疗RM-NPC具有良好的抗肿瘤活性，且毒副反应可控。应谨慎选择重复放疗且距最后一次放疗间隔时间小于12个月的患者进行抗血管生成治疗。MRGPRF表达和连续ctDNA监测可以识别从联合治疗中获益的患者。试用注册：ClinicalTrials.gov：NCT 04073784。
Background: The role of a triple combination of gemcitabine (chemo-therapy) plus apatinib (anti-vascular endothelial growth factor [VEGFR]) and toripalimab (anti-PD-1) (GAT) in recurrent/metastatic nasopharyn-geal carcinoma (RM-NPC) is unclear.Methods: Between August 2019 and April 2020, 41 patients with RM-NPC were enrolled and received GAT for up to 6 cycles followed by apatinib and toripalimab. The primary endpoint was the safety. The sec-ondary endpoints included the objective response rate (ORR) and pro-gression-free survival (PFS). Integrated genomic and transcriptional an-alyses were conducted to identify the patients who benefited in response to this novel combination therapy.Findings: As of April 1, 2022, treatment-related grade 3 or 4 adverse events (AEs) occurred in 23 of 41 patients (56.1%, 95% confidence inter-val [CI] 4 1%-70.1%). G3-4 nasopharyngeal necrosis was observed in 9 (9/41, 21.9%) patients. High-risk factors for necrosis included repeated radiotherapy and an interval of less than 12 months from the last radio-therapy. The ORR was 90.2% (95% CI: 76.9%-97.2%). The median PFS was 25.8 months (95% CI: not reached (NR)-NR), and the 24-month PFS rate was 50.7% (95% CI: 34.0%-6 7.4%). MAS-related GPR family member F (MRGPRF) high expression in tumors correlated with poor PFS from the GAT therapy, characterized by high epithelial mesen-chymal transition signatures. Serial circulating tumor DNA (ctDNA) sequencing could predict PFS outcomes to combination therapy.Conclusions: GAT therapy exhibits a promising antitumor activity and manageable toxicities in patients with RM-NPC. Patients with repeated radiotherapy and an interval of less than 12 months from the last radio-therapy should be carefully selected for antiangiogenic therapies. MRGPRF expression and serial ctDNA monitoring could identify pa-tients that derive benefits from the combination therapy. Trial Registration: ClinicalTrials.gov: NCT04073784.