State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2022 Nov;13(21):2951-2959. doi: 10.1111/1759-7714.14635. Epub 2022 Sep 20.
The switch/sucrose nonfermentable complex mutations (SWI/SNF-mut) are common in non-small cell lung cancer (NSCLC). However, the association of SWI/SNF-mut with the clinical outcomes of immune checkpoint inhibitors (ICIs), particularly of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), has not been established.
We retrospectively collected data of patients at Cancer Hospital Chinese Academy of Medical Sciences. Patients with advanced NSCLC who received programmed cell death protein-1 or programmed cell death ligand 1 (PD-[L]1) inhibitors were included in cohort 1 and those with EGFR mutations (EGFR-mutant) received EGFR-TKIs monotherapy were included in cohort 2. Two reported Memorial Sloan-Kettering Cancer Center (MSKCC) cohorts received immunotherapy alone used as the validation for cohort 1. We analyzed the relationship between SWI/SNF alterations and clinical outcomes in each cohort.
In total, 1162 patients were included, of which 230 patients (19.8%) were identified as SWI/SNF-mut with the most common genetic alterations being ARID1A (33.4%) and SMARCA4 (28.3%). In cohort 1 (n = 146), patients with co-mutations of SWI/SNF and Kirsten rat sarcoma oncogene (KRAS) (SWI/SNFmutKRASmut, n = 18) had significantly prolonged progression-free survival (PFS) (8.6 m vs. 1.9 m; hazard ratio [HR], 0.31; 95% confidence intervals [CI], 0.11-0.83; p = 0.032) to PD-(L)1 inhibitors monotherapy, which was consistent with the MSKCC cohorts (not reach [NR] vs. 6.3 m; HR, 0.36, 95% CI, 0.15-0.82; p = 0.016). In cohort 2 (n = 205), ARID1A-mut (n = 16) was associated with improved PFS after EGFR-TKIs (20.6 m vs. 11.2 m; HR, 0.47, 95% CI, 0.27-0.94; p = 0.023).
In advanced NSCLC, patients with SWI/SNFmutKRASmut seem to benefit more from ICIs. Furthermore, ARID1A-mut may provide a protective effect to EGFR-TKIs in EGFR-mutant patients. However, this is a retrospective single-institution analysis that requires further validation by large prospective studies.
开关/蔗糖非发酵复合物突变（SWI/SNF-mut）在非小细胞肺癌（NSCLC）中较为常见。然而，SWI/SNF-mut 与免疫检查点抑制剂（ICIs），特别是表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的临床结局之间的关联尚未确定。
我们回顾性收集了中国医学科学院肿瘤医院患者的数据。接受程序性死亡蛋白-1 或程序性死亡配体 1（PD-[L]1）抑制剂治疗的晚期 NSCLC 患者纳入队列 1，接受 EGFR 突变（EGFR-mutant）的患者接受 EGFR-TKIs 单药治疗纳入队列 2。两个已报道的 Memorial Sloan-Kettering 癌症中心（MSKCC）队列单独接受免疫治疗，作为队列 1 的验证。我们分析了每个队列中 SWI/SNF 改变与临床结局之间的关系。
共纳入 1162 例患者，其中 230 例（19.8%）被鉴定为 SWI/SNF-mut，最常见的遗传改变为 ARID1A（33.4%）和 SMARCA4（28.3%）。在队列 1（n=146）中，SWI/SNF 和 Kirsten 大鼠肉瘤癌基因（KRAS）共突变（SWI/SNFmutKRASmut，n=18）的患者接受 PD-（L）1 抑制剂单药治疗的无进展生存期（PFS）显著延长（8.6m 比 1.9m；风险比[HR]，0.31；95%置信区间[CI]，0.11-0.83；p=0.032），这与 MSKCC 队列一致（未达到[NR]比 6.3m；HR，0.36，95%CI，0.15-0.82；p=0.016）。在队列 2（n=205）中，ARID1A-mut（n=16）与 EGFR-TKIs 后 PFS 改善相关（20.6m 比 11.2m；HR，0.47，95%CI，0.27-0.94；p=0.023）。
在晚期 NSCLC 中，SWI/SNFmutKRASmut 患者似乎从 ICIs 中获益更多。此外，ARID1A-mut 可能为 EGFR-TKIs 治疗 EGFR-mutant 患者提供保护作用。然而，这是一项回顾性单中心分析，需要进一步的大样本前瞻性研究验证。
