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Durvalumab 用于不可切除的 III 期非小细胞肺癌放化疗后的治疗。

Durvalumab After Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer.

机构信息

Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston.

AstraZeneca, Gaithersburg, Maryland.

出版信息

JAMA Netw Open. 2024 Apr 1;7(4):e247542. doi: 10.1001/jamanetworkopen.2024.7542.

Abstract

IMPORTANCE

The PACIFIC trial established consolidation durvalumab as the standard of care following chemoradiotherapy (CRT) for patients with unresectable stage III non-small cell lung cancer (NSCLC). Understanding its benefit in routine US clinical practice is critical.

OBJECTIVE

To report characteristics, treatment patterns, and outcomes of patients who did or did not receive durvalumab.

DESIGN, SETTING, AND PARTICIPANTS: Two prespecified cohorts were curated in this retrospective cohort study (SPOTLIGHT). Deidentified patient-level data from a US database (Flatiron Health) were analyzed. Patients had unresectable stage III NSCLC, were diagnosed on or after January 1, 2011, had 2 or more visits on or afterward, and received CRT. Data were analyzed from May 2021 to October 2023.

EXPOSURES

Patients started durvalumab after CRT (durvalumab cohort) or ended CRT without durvalumab (nondurvalumab cohort) by June 30, 2019, to allow 15 or more months of follow-up from CRT end.

MAIN OUTCOMES AND MEASURES

End points included progression-free survival (PFS), overall survival (OS), time to first subsequent therapy or death (TFST), and time to distant metastasis or death (TTDM).

RESULTS

The durvalumab cohort included 332 patients (median [IQR] age, 67.5 [60.8-74.0] years; 187 were male [56.3%], 27 were Black [8.7%], 33 were other races [10.7%], and 249 were White [80.6%]) and the nondurvalumab cohort included 137 patients (median (IQR) age, 70.0 [64.0-75.0] years; 89 [65.0%] were male, 11 [8.9%] were Black, 19 [15.4%] were other races, and 93 [75.6%] were White). Most patients had a smoking history (durvalumab, 316 patients [95.2%] and nondurvalumab, 132 patients [96.4%]) and Eastern Cooperative Oncology Group performance status 0 through 1 (durvalumab, 251 patients [90.9%] and nondurvalumab, 88 patients [81.5%]). Median (IQR) CRT duration was 1.6 (1.4-1.8) months for the durvalumab cohort and 1.5 (1.4-1.8) months for the nondurvalumab cohort. Median time to durvalumab discontinuation was 9.5 months (95% CI, 7.8-10.6 months). Median TFST and TTDM were not reached (NR) in the durvalumab cohort and 8.3 months (95% CI, 4.8-11.8 months) and 11.3 months (95% CI, 6.4-14.5 months), respectively, in the nondurvalumab cohort. Median PFS and OS were 17.5 months (95% CI, 13.6-24.8 months) and NR in the durvalumab cohort and 7.6 months (95% CI, 5.2-9.8 months) and 19.4 months (95% CI, 11.7-24.0 months) in the nondurvalumab cohort. In Cox regression analyses of patients who completed concurrent CRT without progression, durvalumab was associated with a lower risk of progression or death (hazard ratio [HR], 0.36; 95% CI, 0.26-0.51) and lower risk of death (HR, 0.27; 95% CI, 0.16-0.43), adjusted for prior platinum agent and patient characteristics.

CONCLUSIONS AND RELEVANCE

In this cohort study, findings were consistent with PACIFIC, and durvalumab was associated with a lower risk of progression and/or death. Further investigation is warranted to explain why patients did not receive durvalumab after its approval.

摘要

重要性

PACIFIC 试验确立了巩固 durvalumab 作为不可切除 III 期非小细胞肺癌 (NSCLC) 患者放化疗后标准治疗的地位。了解其在美国常规临床实践中的益处至关重要。

目的

报告接受或未接受 durvalumab 治疗的患者的特征、治疗模式和结局。

设计、设置和参与者:本回顾性队列研究 (SPOTLIGHT) 中 curated 了两个预设队列。分析了来自美国数据库(Flatiron Health)的匿名患者水平数据。患者患有不可切除的 III 期 NSCLC,诊断日期为 2011 年 1 月 1 日或之后,且有 2 次或更多次就诊,且接受了 CRT。数据于 2021 年 5 月至 2023 年 10 月进行分析。

暴露

患者在 2019 年 6 月 30 日之前开始接受 durvalumab 治疗(durvalumab 队列)或结束 CRT 而未接受 durvalumab 治疗(nondurvalumab 队列),以允许从 CRT 结束起有 15 个月或更长时间的随访。

主要结局和测量

终点包括无进展生存期 (PFS)、总生存期 (OS)、首次后续治疗或死亡时间 (TFST) 和远处转移或死亡时间 (TTDM)。

结果

durvalumab 队列包括 332 名患者(中位 [IQR] 年龄,67.5 [60.8-74.0] 岁;187 名男性 [56.3%],27 名黑人 [8.7%],33 名其他种族 [10.7%],249 名白人 [80.6%]),nondurvalumab 队列包括 137 名患者(中位 [IQR] 年龄,70.0 [64.0-75.0] 岁;89 名 [65.0%] 为男性,11 名 [8.9%] 为黑人,19 名 [15.4%] 为其他种族,93 名 [75.6%] 为白人)。大多数患者有吸烟史(durvalumab 队列 316 名患者 [95.2%],nondurvalumab 队列 132 名患者 [96.4%])和 Eastern Cooperative Oncology Group 表现状态 0 至 1(durvalumab 队列 251 名患者 [90.9%],nondurvalumab 队列 88 名患者 [81.5%])。中位(IQR)CRT 持续时间为 durvalumab 队列 1.6(1.4-1.8)个月,nondurvalumab 队列 1.5(1.4-1.8)个月。durvalumab 停药的中位时间为 9.5 个月(95%CI,7.8-10.6 个月)。在 durvalumab 队列中,中位 TFST 和 TTDM 未达到(NR),分别为 8.3 个月(95%CI,4.8-11.8 个月)和 11.3 个月(95%CI,6.4-14.5 个月),在 nondurvalumab 队列中,分别为 7.6 个月(95%CI,5.2-9.8 个月)和 19.4 个月(95%CI,11.7-24.0 个月)。在未进展的同期 CRT 完成患者的 Cox 回归分析中,durvalumab 与较低的进展或死亡风险(风险比 [HR],0.36;95%CI,0.26-0.51)和较低的死亡风险(HR,0.27;95%CI,0.16-0.43)相关,调整了先前的铂类药物和患者特征。

结论和相关性

在这项队列研究中,结果与 PACIFIC 一致,durvalumab 与较低的进展和/或死亡风险相关。需要进一步调查以解释为什么在其批准后患者没有接受 durvalumab。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4729/11036139/6a05b857daff/jamanetwopen-e247542-g001.jpg

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