本文由小咖机器人翻译整理

期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2023.24735

摘要内容如下：

重要性

辅助和新辅助免疫治疗改善了早期非小细胞肺癌（NSCLC）患者的临床结果。然而，检查点抑制与化疗的最佳组合仍然未知。

目的

确定与单独化疗相比，Toripalimab联合以铂为基础的化疗是否会改善II期或III期可切除NSCLC患者的无事件生存率和主要病理反应。

设计、设置和参与者

该随机临床试验于2020年3月12日至2023年6月19日在中国50家参与医院纳入了II期或III期可切除NSCLC（非鳞状NSCLC无EGFR或ALK改变）患者。本次中期分析的数据截止日期为2022年11月30日。

干预措施

患者以1:1的比例随机接受每3周一次的240mg托利帕利单抗或安慰剂联合以铂为基础的化疗，手术前3个周期，手术后1个周期，然后仅接受托利帕利单抗（240mg）或安慰剂，每3周一次，最多13个周期。

主要成果和措施

主要结果是无事件生存率（由研究者评估）和主要病理反应率（通过盲法、独立的病理审查评估）。次要转归包括病理完全缓解率（通过盲法、独立病理审查评估）和不良事件。

结果

在随机分组的501例患者中，404例为III期NSCLC（202例为Toripalimab+化疗组，202例为安慰剂+化疗组），97例为II期NSCLC，被排除在本中期分析之外。中位年龄为62岁（IQR，56-65岁），92%患者为男性，中位随访时间为18.3个月（IQR，12.7-22.5个月）。对于无事件生存期的主要转归，Toripalimab组的中位生存期无法估计（95%CI，24.4个月-无法估计），而安慰剂组的中位生存期为15.1个月（95%CI，10.6-21.9个月）（风险比，0.40[95%CI，0.28-0.57]，P<.001）。Toripalimab组的主要病理缓解率（另一个主要转归）为48.5%（95%CI，41.4%-55.6%），安慰剂组为8.4%（95%CI，5.0%-13.1%）（组间差异，40.2%[95%CI，32.2%-48.1%]，P<.001）。Toripalimab组的病理完全缓解率（次要结果）为24.8%（95%CI，19.0%-31.3%），安慰剂组为1.0%（95%CI，0.1%-3.5%）（组间差异，23.7%[95%CI，17.6%-29.8%]）。Toripalimab组的免疫相关不良事件发生率更高。未发现与治疗相关的意外毒性作用。3级或更高级别不良事件、致命不良事件和导致中断治疗的不良事件的发生率在两组之间具有可比性。

结论和相关性

在围手术期化疗中加入Toripalimab可显著改善可切除的III期NSCLC患者的无事件生存率，并且这种治疗策略具有可控的安全性。

英文原文如下：

Abstracts

Importance  Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown.

Objective  To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone.

Design, Setting, and Participants  This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022.

Interventions  Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles.

Main Outcomes and Measures  The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events.

Results  Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups.

Conclusions and Relevance  The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile.

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