Objectives

Second-line immune checkpoint inhibition (ICI) was recently shown to have a survival advantage over placebo in malignant pleural mesothelioma (MPM), but the survival comparison to chemotherapy in patients with MPM receiving routine clinical care is unknown. Our objective was to examine the effectiveness of second-line ICI versus chemotherapy on overall survival (OS) outcomes in real-world patients with advanced MPM.

Materials and Methods

We performed a multicenter retrospective cohort study of real-world adult patients with advanced MPM who received first-line platinum-based chemotherapy and at least two total lines of systemic therapy. Patients received either second-line chemotherapy (gemcitabine and/or vinorelbine) or ICI therapy (pembrolizumab or nivolumab ± ipilimumab). The primary outcome was OS, defined as the time from second-line therapy initiation to death or end of the observation period. We used Kaplan-Meier methods and Cox proportional hazards modeling with adjustment for relevant patient demographic and clinical variables to compare OS between the two second-line treatment groups.

Results

Of the 176 patients with MPM, the median age was 75 years (IQR: 69–79.5 years), and most were white (77%), male (74%), and had epithelioid histology (67%). Thirty-five percent (61) received second-line chemotherapy and 65% (1 1 5) ICI therapy (80 pembrolizumab, 31 nivolumab, and 4 nivolumab + ipilimumab). Treatment with ICI was associated with significantly longer median OS compared to chemotherapy (8.7 vs 5.0 months, p=0.001; adjusted hazard ratio: 0.52, 95% CI: 0.34–0.81). The estimated 12-month OS probability was 36.7% (95% CI: 27.6%-45.8%) and 15.6% (95% CI: 7.7%-26.1%) in the ICI and chemotherapy groups, respectively.

Conclusion

In this “real-world” population of patients with MPM, treatment with ICI was associated with improved OS outcomes compared to chemotherapy in the second-line setting, in contrast with a recent clinical trial. Our findings suggest that ICI may benefit patients with advanced MPM and progression after initial platinum-based chemotherapy.

中文翻译：

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二线免疫检查点抑制剂治疗与化疗治疗恶性胸膜间皮瘤的疗效比较

 目标

最近显示，二线免疫检查点抑制 (ICI) 在恶性胸膜间皮瘤 (MPM) 治疗中比安慰剂具有生存优势，但接受常规临床护理的 MPM 患者与化疗的生存比较尚不清楚。我们的目的是检查二线 ICI 与化疗对现实世界晚期 MPM 患者总生存 (OS) 结果的有效性。

 材料和方法

我们对现实世界中接受一线铂类化疗和至少两种全身治疗的晚期 MPM 成年患者进行了多中心回顾性队列研究。患者接受二线化疗（吉西他滨和/或长春瑞滨）或 ICI 治疗（派姆单抗或纳武单抗 ± 伊匹单抗）。主要结局是 OS，定义为从二线治疗开始到死亡或观察期结束的时间。我们使用 Kaplan-Meier 方法和 Cox 比例风险模型，并调整相关患者人口统计和临床变量来比较两个二线治疗组之间的 OS。

 结果

在 176 名 MPM 患者中，中位年龄为 75 岁（IQR：69-79.5 岁），大多数为白人（77%）、男性（74%）和上皮样组织学（67%）。 35% (61) 接受二线化疗，65% (1 1 5) ICI 治疗（80 派姆单抗、31 纳武单抗和 4 纳武单抗 + 易普利姆玛）。与化疗相比，ICI 治疗与中位 OS 显着延长相关（8.7 个月 vs 5.0 个月，p=0.001；调整后风险比：0.52，95% CI：0.34-0.81）。 ICI 组和化疗组的估计 12 个月 OS 概率分别为 36.7%（95% CI：27.6%-45.8%）和 15.6%（95% CI：7.7%-26.1%）。

 结论

与最近的一项临床试验相比，在这个“真实世界”的 MPM 患者群体中，与二线化疗相比，ICI 治疗与 OS 结局改善相关。我们的研究结果表明，ICI 可能有益于晚期 MPM 和初始铂类化疗后进展的患者。