一线阿替利珠单抗联合卡铂和依托泊苷治疗广泛期小细胞肺癌的长期生存者的临床和分子特征。
Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide.
机构信息
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China.
出版信息
Lung Cancer. 2023 Dec;186:107418. doi: 10.1016/j.lungcan.2023.107418. Epub 2023 Oct 31.
OBJECTIVES
In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.
MATERIALS AND METHODS
Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months post randomization. A generalized linear model was used to evaluate the odds of living ≥ 18 months. Differential gene expression was analyzed using RNA-sequencing data in LTS and non-LTS. OS was assessed by T-effector and B-cell gene signature expression. Distribution of SCLC transcriptional subtypes was assessed in LTS and non-LTS.
RESULTS
More LTS were in the atezolizumab arm (34%) than in the placebo arm (20%). The odds ratio for living ≥ 18 months in the atezolizumab arm versus the placebo arm was 2.1 (P < 0.03). Enhanced immune-related signaling was seen in LTS in both arms. Exploratory OS analyses showed atezolizumab treatment benefit versus placebo across T-effector and B-cell gene signature expression subgroups. A higher proportion of LTS than non-LTS in both arms had the SCLC-I subtype; this difference was particularly pronounced in the atezolizumab arm.
CONCLUSION
These exploratory analyses suggest that long-term survival is more likely with atezolizumab than placebo in ES-SCLC, confirming the treatment benefit of the IMpower133 regimen.
CLINICALTRIAL
gov Identifier: NCT02763579.
目的
在 I 期/III 期 IMpower133 研究中，一线阿特珠单抗联合卡铂和依托泊苷（CP/ET）治疗广泛期小细胞肺癌（ES-SCLC）与安慰剂联合 CP/ET 相比，显著改善了总生存期（OS）和无进展生存期（PFS）。我们探讨了 IMpower133 中与长期生存相关的患者和疾病特征，以及差异基因表达与 SCLC-A（ASCL1 驱动）、SCLC-N（NEUROD1 驱动）、SCLC-P（POU2F3 驱动）和 SCLC-炎症（SCLC-I）转录亚型与长期生存的关联。
材料和方法
未经治疗的 ES-SCLC 患者按 1:1 随机分为四组，每组接受 21 天周期的 CP/ET 联合阿特珠单抗或安慰剂。长期幸存者（LTS）定义为随机分组后生存≥18 个月的患者。使用广义线性模型评估生存≥18 个月的可能性。使用 LTS 和非-LTS 的 RNA-seq 数据分析差异基因表达。通过 T 效应细胞和 B 细胞基因特征表达评估 OS。在 LTS 和非-LTS 中评估 SCLC 转录亚型的分布。
结果
阿特珠单抗组的 LTS 患者（34%）多于安慰剂组（20%）。阿特珠单抗组生存≥18 个月的优势比（OR）为 2.1（P<0.03）。在两个治疗组中，LTS 中均观察到增强的免疫相关信号。探索性 OS 分析显示，阿特珠单抗治疗与安慰剂相比，在 T 效应细胞和 B 细胞基因特征表达亚组中均有获益。两个治疗组中，LTS 的 SCLC-I 亚型比例均高于非-LTS；阿特珠单抗组的这一差异更为显著。
结论
这些探索性分析表明，ES-SCLC 中阿特珠单抗的长期生存获益高于安慰剂，证实了 IMpower133 方案的治疗获益。
临床试验
gov 标识符：NCT02763579。
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