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：

新輔助化療免疫治療在可切除的IIIA期NSCLC中顯示出高度有效。現在我們提供長期生存率數據。

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：

這是一個開放的，多中心的，單臂2期臨床試驗，在該實驗中，患者的組織學或細胞學上分期為III a 期NSCLC腫瘤，在東部合作組表現狀態為0或1。多學科臨床團隊認為局部可手術切除的患者，接受新輔助靜脈紫杉醇(200 mg/m2)和卡鉑治療(曲線6下麵積;6 mg/mL / min) +尼魯單抗(360 mg)，在每個21天周期的第1天，手術切除前3個周期，隨後輔助靜脈尼魯單抗單藥治療1年(每2周240 mg，持續4個月，隨後每4周480 mg，持續8個月)。

在這裏，我們報告了36個月和42個月的無進展生存期(PFS)和總生存期(OS)，評估對象為改良意向治療人群(ITT)，包括所有接受新輔助治療的患者，以及按方案進行的人群(PP)。包括所有切除腫瘤並接受至少一個周期輔助治療的患者。

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.

結果：

中位隨訪時間為37.9個月(95%CI: 36.7-40.7)， 36個月成熟度94%。ITT人群(N=46)中，37例患者接受後續輔助治療，構成PP人群。

其中27例(58.7%)患者完成了輔助治療(16個周期)，10例(21.7%)患者接受了3 ~ 15個周期的輔助治療，9例(19.6%)患者未接受輔助治療。在數據截止時(2021年3月)，ITT人群中有14例患者診斷為病情進展，9例死亡。其中，3例死亡與未接受手術並出現疾病進展的患者有關，4例死亡與接受手術並出現疾病進展的患者有關，其餘2例死亡與被診斷為無症狀但死於covid - 19感染的患者有關。值得注意的是，在不能接受手術的患者中(N=5)，其中1人仍然活著，沒有任何疾病症狀。

ITT組36個月和42個月的PFS（無進展生存期）分別為69.6% (95%CI: 54.1-80.7)。同樣，在36歲和42歲的PP人群中，PFS均為81.1% (95%CI: 64.4-90.5)。改良後的ITT人群中36個月和42個月存活的患者比例分別為81.86% (95%CI: 66.8-90.6)和78.94% (95%CI: 63.1-88.6)。同樣，PP人群36個月和42個月的OS分別為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.

結論：

長期生存率數據明確支持了，尼魯單抗聯合鉑基化療在可切除的IIIA期NSCLC患者中的療效。