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不同抗程序性死亡蛋白-1(PD-1)检查点联合策略用于一线晚期非小细胞肺癌治疗的经验——伊翁·基里库ță肿瘤研究所的经验

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment-The Experience of Ion Chiricuță Oncology Institute.

作者信息

Preda Alexandra-Cristina, Ciuleanu Tudor-Eliade, Todor Nicolae, Vlad Cătălin, Iancu Dana Ioana, Mocan Cristina, Bandi-Vasilica Mariana, Albu Florina, Todor-Bondei Irina Mihaela, Hapca Mădălina Claudia, Kubelac Milan-Paul, Kubelac-Varro Adelina Dadiana

机构信息

Oncology Institute Prof. Dr. Ion Chiricuță, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania.

Iuliu Hațieganu University of Medicine and Pharmacy, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania.

出版信息

Cancers (Basel). 2024 May 26;16(11):2022. doi: 10.3390/cancers16112022.

Abstract

PURPOSE

Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute.

METHODS

A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors.

RESULTS

Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months ( = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months ( = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% ( = 0.22). Older age, impaired PS (2 versus 0-1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2).

CONCLUSIONS

Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.

摘要

目的

在多项临床试验中,抗程序性死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)药物与铂类化疗或另一种检查点抑制剂(联合或不联合短疗程或全疗程铂类双联化疗)的不同联合治疗模式已被证明优于单纯化疗,但这些策略尚未直接比较。本研究的目的是报告在Ion Chiricuță肿瘤研究所连续队列中接受治疗的一系列患者采用不同免疫治疗联合方案的真实世界数据结果。

方法

共有122例患者先后纳入三个队列:(1A)纳武利尤单抗+伊匹木单抗(18例患者),(1B)纳武利尤单抗+伊匹木单抗+短疗程化疗(33例患者),以及(2)帕博利珠单抗+全疗程化疗(71例患者)。终点包括总生存期(OS)、无进展生存期(PFS)、客观缓解率(ORR)以及预后因素的单因素和多因素探索性分析。

结果

连续队列1A、1B和2的中位随访时间分别为83个月、59个月和14.2个月。所有患者的中位OS和PFS分别为22.2个月和11.5个月,2年精算OS和PFS分别为49%和35%。对于纳武利尤单抗+伊匹木单抗(队列1A和1B)与帕博利珠单抗联合方案(队列2),中位OS为14个月对24.8个月(P = 0.18),2年精算生存率为42%对53%;中位PFS为8.6个月对12.7个月(P = 0.41),2年精算PFS为34%对35%;缓解率为33.3%对47.9%(P = 0.22)。年龄较大、体能状态受损(2分对0 - 1分)、免疫治疗第一个月使用皮质类固醇治疗以及中性粒细胞与淋巴细胞比值>3.81是生存多因素分析中的独立不良预后因素(限于2年随访)。队列1A和1B的5年长期生存率分别为30.5%和18.8%(队列2随访不足)。

结论

使用不同免疫治疗联合策略的疗效结果令人鼓舞,在2年时各方案之间无显著差异。我们系列研究中的真实世界疗效和长期结果与相应注册试验中报告的结果一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ace7/11171289/7d99bc597f46/cancers-16-02022-g001.jpg

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