Cheng Ying, Zhou Qing, Han Baohui, Fan Yun, Shan Li, Chang Jianhua, Sun Si, Fang Jian, Chen Yuan, Sun Jianguo, Wu Gang, Mann Helen, Naicker Kirsha, Shire Norah, Mok Tony, de Castro Gilberto
Jilin Cancer Hospital, Changchun, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Lung Cancer. 2023 Apr;178:87-95. doi: 10.1016/j.lungcan.2023.01.013. Epub 2023 Feb 1.
The phase 3 NEPTUNE study (NCT02542293) evaluated first-line durvalumab plus tremelimumab (DT) versus chemotherapy for metastatic NSCLC. Prespecified exploratory analyses were conducted in an extended cohort enrolled in China.
Patients were randomized (1:1) to DT or standard chemotherapy, stratified by PD-L1 tumor cell (TC) expression (≥25 % vs < 25 %), histology, and smoking history. The primary analysis for this cohort was overall survival (OS) in patients with PD-L1 TC < 1 %. Secondary analyses included OS and progression-free survival (PFS) in the ITT population and PD-L1 subgroups, and safety. No alpha was allocated to these cohort analyses (data cut-off, 21-September-2020).
78 and 82 patients were randomized to DT and chemotherapy, respectively; 26 and 29 had PD-L1 TC < 1 % (median follow-up, 31.2 and 29.7 months [censored patients]). Among patients with PD-L1 TC < 1 %, OS favored DT versus chemotherapy (HR 0.60; 95 % CI, 0.32-1.11), with medians of 15.0 months (95 % CI, 10.5-27.4) and 11.7 months (95 % CI, 8.6-20.5), respectively; 24-month rates were 36.0 % (95 % CI, 18.2-54.2) and 17.9 % (95 % CI, 6.5-33.7). In the ITT population, OS was prolonged with DT versus chemotherapy (HR 0.70; 95 % CI, 0.48-1.02); medians were 20.0 and 14.1 months and 24-month rates were 44.2 % and 30.4 %. PFS was similar in the PD-L1 TC < 1 % (HR 1.13; 95 % CI, 0.59-2.14) and ITT (HR 0.95; 95 % CI, 0.66-1.36) populations; 12-month rates were 15.6 % versus 11.3 % and 23.9 % versus 16.6 %. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 31.2 % with DT and 52.6 % with chemotherapy; 3.9 % versus 10.3 % discontinued due to TRAEs.
In exploratory analyses, first-line DT showed a trend towards improved OS versus chemotherapy among Chinese patients in the PD-L1 TC < 1 % population and ITT population, with 24-month OS and 12-month PFS rates indicating benefit in survival curve tails. DT was well tolerated with no new safety signals.
3期NEPTUNE研究（NCT02542293）评估了一线度伐利尤单抗联合曲美木单抗（DT）与化疗治疗转移性非小细胞肺癌（NSCLC）的疗效。在中国入组的一个扩大队列中进行了预先设定的探索性分析。
患者按1:1随机分为DT组或标准化疗组，按程序性死亡配体1（PD-L1）肿瘤细胞（TC）表达（≥25% 与 <25%）、组织学和吸烟史进行分层。该队列的主要分析是PD-L1 TC<1%患者的总生存期（OS）。次要分析包括意向性治疗（ITT）人群和PD-L1亚组中的OS和无进展生存期（PFS），以及安全性。这些队列分析未设定α值（数据截止日期为2020年9月21日）。
分别有78例和82例患者被随机分配至DT组和化疗组；26例和29例患者的PD-L1 TC<1%（中位随访时间分别为31.2个月和29.7个月[删失患者]）。在PD-L1 TC<1%的患者中，DT组的OS优于化疗组（风险比[HR]为0.60；95%置信区间[CI]为0.32 - 1.11），中位生存期分别为15.0个月（95%CI为10.5 - 27.4）和11.7个月（95%CI为8.6 - 20.5）；24个月生存率分别为36.0%（95%CI为18.2 - 54.2）和17.9%（95%CI为6.5 - 33.7）。在ITT人群中，DT组的OS较化疗组长（HR为0.70；95%CI为0.48 - 1.02）；中位生存期分别为20.0个月和14.1个月，24个月生存率分别为44.2%和30.4%。在PD-L1 TC<1%人群（HR为1.13；95%CI为0.59 - 2.14）和ITT人群（HR为0.95；95%CI为0.66 - 1.36）中，PFS相似；12个月发生率分别为15.6%对11.3%以及23.9%对16.6%。3/4级治疗相关不良事件（TRAEs）在DT组中的发生率为31.2%，在化疗组中的发生率为52.6%；因TRAEs停药的比例分别为3.9%和10.3%。
在探索性分析中，对于中国PD-L1 TC<1%人群和ITT人群，一线DT与化疗相比显示出OS改善的趋势，24个月OS率和12个月PFS率表明在生存曲线尾部有获益。DT耐受性良好，无新的安全信号。
