Background

A taxane plus ramucirumab as second-line therapy followed by a checkpoint inhibitor (CPI) in third line has become a standard treatment strategy for advanced gastric cancer.

Objective

Herein, we investigated the impact of prior ramucirumab use on the efficacy of third-line immunotherapy and performed an exploratory analysis to identify potential biomarkers for the success of immunotherapy.

Patients and Methods

We retrospectively analyzed patients receiving CPI as a third-line treatment for advanced gastric cancer between January 2015 and March 2019. Clinicopathologic data, including patient characteristics, histopathologic reports, and treatment types and outcomes, were reviewed.

Results

Of the 74 patients included in this study, 45 (61%) received nivolumab and 29 (39%) received pembrolizumab as a third-line CPI. For second-line therapy, 41 patients (55%) were treated with ramucirumab plus a taxane, and 33 (45%) received a chemotherapy regimen without ramucirumab. The disease control rates of CPIs were not statistically different according to prior use of ramucirumab. The overall survival (OS) with CPI was higher in patients receiving second-line therapy without ramucirumab compared with those receiving ramucirumab and taxane (5.6 vs 4.8 months, HR 0.56, 95% confidence interval [CI] 0.33–0.96; p = 0.03); however, this was not significant in a multivariate analysis. Patients achieving a response to second-line ramucirumab and a taxane showed greater benefit from subsequent CPI treatment compared with those not achieving a response (median OS 9.9 vs 2.3 months, HR 0.20, 95% CI 0.07–0.54; p < 0.001) as found in an exploratory analysis. Multivariate analysis also showed that prior response to ramucirumab and a taxane was an independent prognostic factor of OS with third-line CPI.

Conclusions

Response to ramucirumab and a taxane as a second-line treatment is an important prognostic marker for OS with subsequent third-line CPI. This data might provide useful information when applying CPIs as third-line therapies in advanced gastric cancer patients.

中文翻译：

---

先前使用雷莫芦单抗对晚期胃癌患者检查点抑制剂治疗结果的影响。

 背景

紫杉烷联合雷莫芦单抗作为二线治疗，随后检查点抑制剂（CPI）作为三线治疗已成为晚期胃癌的标准治疗策略。

 客观的

在此，我们研究了先前使用雷莫芦单抗对三线免疫疗法疗效的影响，并进行了探索性分析，以确定免疫疗法成功的潜在生物标志物。

 患者和方法

我们回顾性分析了 2015 年 1 月至 2019 年 3 月期间接受 CPI 作为晚期胃癌三线治疗的患者。回顾了临床病理数据，包括患者特征、组织病理学报告以及治疗类型和结果。

 结果

在本研究纳入的 74 名患者中，45 名 (61%) 接受纳武单抗治疗，29 名 (39%) 接受派姆单抗作为三线 CPI。对于二线治疗，41 名患者 (55%) 接受雷莫芦单抗加紫杉烷治疗，33 名患者 (45%) 接受不含雷莫芦单抗的化疗方案。根据之前使用雷莫芦单抗的情况，CPI 的疾病控制率没有统计学差异。与接受雷莫芦单抗和紫杉烷治疗的患者相比，接受不使用雷莫芦单抗的二线治疗的患者的 CPI 总生存期 (OS) 较高（5.6 个月与 4.8 个月，HR 0.56，95% 置信区间 [CI] 0.33–0.96； p = 0.03） ;然而，这在多变量分析中并不显着。结果显示，与未获得缓解的患者相比，对二线雷莫芦单抗和紫杉烷获得缓解的患者从后续 CPI 治疗中获益更大（中位 OS 9.9 个月与 2.3 个月，HR 0.20，95% CI 0.07–0.54； p < 0.001）在探索性分析中。多变量分析还表明，先前对雷莫芦单抗和紫杉烷的反应是三线 CPI 的 OS 的独立预后因素。

 结论

对雷莫芦单抗和紫杉烷作为二线治疗的反应是 OS 和随后的三线 CPI 的重要预后标志。当将 CPI 作为晚期胃癌患者的三线疗法时，这些数据可能会提供有用的信息。