Long Term Survival in Operable Stage Iiia Nsclc Patients Treated With Neoadjuvant Nivolumab Plus Chemotherapy - Nadim Study

Introduction

Neoadjuvant chemoimmunotherapy been shown to be highly effective in resectable stage IIIA NSCLC. Now we provide long term survival data

摘要：

新辅助化疗免疫治疗在可切除的IIIA期NSCLC中显示出高度有效。现在我们提供长期生存率数据。

Methods

This was an open-label, multicentre, single-arm phase 2 trial in which patients with histologically or cytologically documented stage IIIA NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 and who were deemed locally to be surgically resectable by a multidisciplinary clinical team were treated with neoadjuvant intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6; 6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). Here we report progression-free survival (PFS) and Overall survival (OS) at 36 and 42 months, assessed in the modified intention-to-treat population (ITT), which included all patients who received neoadjuvant treatment, and in the per-protocol population (PP), which included all patients who had tumour resection and received at least one cycle of adjuvant treatment.

研究方法：

这是一个开放的，多中心的，单臂2期临床试验，在该实验中，患者的组织学或细胞学上分期为III a 期NSCLC肿瘤，在东部合作组表现状态为0或1。多学科临床团队认为局部可手术切除的患者，接受新辅助静脉紫杉醇(200 mg/m2)和卡铂治疗(曲线6下面积;6 mg/mL / min) +尼鲁单抗(360 mg)，在每个21天周期的第1天，手术切除前3个周期，随后辅助静脉尼鲁单抗单药治疗1年(每2周240 mg，持续4个月，随后每4周480 mg，持续8个月)。

在这里，我们报告了36个月和42个月的无进展生存期(PFS)和总生存期(OS)，评估对象为改良意向治疗人群(ITT)，包括所有接受新辅助治疗的患者，以及按方案进行的人群(PP)。包括所有切除肿瘤并接受至少一个周期辅助治疗的患者。

Results

Median follow-up time was 37.9 months (95%CI: 36.7-40.7), with a 94% maturity at 36 months. Among the ITT population (N=46), 37 patients, constituting the PP population, received subsequent adjuvant therapy.

Of them, 27 (58.7%) patients completed the adjuvant treatment (16 cycles), 10 (21.7%) patients received between 3 and 15 cycles of adjuvant therapy, and 9 (19.6%) patients did not receive adjuvant therapy. At the time of data cutoff (March 2021), progression disease was diagnosed in 14 patients and 9 deaths were recorded in the ITT population. Of these, three deaths corresponded to patients who did not undergo surgery and had disease progression, four deaths corresponded to patients who underwent surgery and had disease progression, and the two remaining deaths corresponded to patients who were diagnosed as being disease free but died from COVID19 infection.

Notably, among patients who could not undergo surgery (N=5), one of them is still alive and with no evidence of disease. PFS at 36 and 42 months in the ITT population were 69.6% (95%CI: 54.1-80.7), in both cases. Similarly, PFS at 36 and 42 in the PP population were 81.1% (95%CI: 64.4-90.5) in both cases. The percentage of patients who were alive at 36 and 42 months in the modified ITT population were 81.86% (95% CI: 66.8-90.6) and 78.94% (95%CI: 63.1-88.6), respectively. Likewise, OS at 36 and 42 months in the PP population was 91.0% (95%CI: 74.2-97.0) and 87.3% (95%CI: 69.3-95.1), respectively.

结果：

中位随访时间为37.9个月(95%CI: 36.7-40.7)， 36个月成熟度94%。ITT人群(N=46)中，37例患者接受后续辅助治疗，构成PP人群。

其中27例(58.7%)患者完成了辅助治疗(16个周期)，10例(21.7%)患者接受了3 ~ 15个周期的辅助治疗，9例(19.6%)患者未接受辅助治疗。在数据截止时(2021年3月)，ITT人群中有14例患者诊断为病情进展，9例死亡。其中，3例死亡与未接受手术并出现疾病进展的患者有关，4例死亡与接受手术并出现疾病进展的患者有关，其余2例死亡与被诊断为无症状但死于covid - 19感染的患者有关。值得注意的是，在不能接受手术的患者中(N=5)，其中1人仍然活着，没有任何疾病症状。

ITT组36个月和42个月的PFS（无进展生存期）分别为69.6% (95%CI: 54.1-80.7)。同样，在36岁和42岁的PP人群中，PFS均为81.1% (95%CI: 64.4-90.5)。改良后的ITT人群中36个月和42个月存活的患者比例分别为81.86% (95%CI: 66.8-90.6)和78.94% (95%CI: 63.1-88.6)。同样，PP人群36个月和42个月的OS分别为91.0% (95%CI: 74.2-97.0)和87.3% (95%CI: 69.3-95.1)。

Conclusion

The efficacy of nivolumab in combination with platinum-based chemotherapy in patients with resectable stage IIIA NSCLC is clearly supported by long term survival data.

结论：

长期生存率数据明确支持了，尼鲁单抗联合铂基化疗在可切除的IIIA期NSCLC患者中的疗效。