Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Emergency Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Int J Cancer. 2020 Jun 1;146(11):3124-3133. doi: 10.1002/ijc.32717. Epub 2019 Nov 1.
This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447-0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.
本研究旨在比较接受免疫治疗的非小细胞肺癌(NSCLC)亚洲和白种人患者在特征和预后方面的差异。我们研究了 390 名接受阿特珠单抗治疗的患者,这些患者来自 POPLAR 或 OAK 试验,分析了亚洲和白种人患者的基线特征、结局和血液样本中的基因突变异质性。亚洲患者的总生存期(OS)长于白种人(中位 OS:18.7 个月 vs. 11.1 个月;p = 0.005)。种族被确定为 OS 的独立预后因素(亚洲 vs. 白种人:风险比 0.647,95%置信区间 0.447-0.936,p = 0.021),与体能状态、组织学、基线最长肿瘤直径总和(BLSLD)和转移部位数量相关。两组在吸烟史、BLSLD、表皮生长因子受体(EGFR)突变频率、程序性死亡配体 1 表达和基于血液的肿瘤突变负担等特征方面也存在差异。STK11、EGFR、KEAP1、POLE、GRM3、ATM 和 STAG2 的血液突变与治疗反应相关,TP53、KEAP1、APC、RB1、CREBBP、EPHA5 和 STAG2 突变与 OS 相关。血液突变谱可区分亚洲和白种人患者,尤其是 EGFR(23.8% vs. 8.5%)、TP53(30.2% vs. 46.9%)和 STK11(1.6% vs. 12.3%)突变(均 p<0.05)。亚洲和白种人患者的不同临床病理特征和突变谱可能解释了 NSCLC 亚洲患者接受阿特珠单抗治疗后结局更好的原因。本研究结果对进一步研究免疫治疗相关的种族差异具有重要意义。