Wu Yanyu, Yin Yu, Crossland Victoria, Vincent Sylvie, Paik Paul K, Lineberry Neil, Faller Douglas V
Takeda Development Center Americas, Inc, Lexington, MA.
Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY.
Clin Lung Cancer. 2022 Sep;23(6):487-497. doi: 10.1016/j.cllc.2022.05.008. Epub 2022 May 11.
NFE2L2 and/or KEAP1 mutations are associated with worse prognosis in all non-small cell lung cancer (NSCLC). We determined real-world survival outcomes and treatment patterns among patients with advanced squamous cell NSCLC by NFE2L2 and KEAP1 mutation status.
A retrospective study (January 2011-December 2018) was conducted using a de-identified US-based clinico-genomic database. Adult patients with advanced squamous cell NSCLC with ≥ 2 in-network visits and comprehensive genomic profiling during the study period were included. Outcomes included real-world progression free survival (rwPFS) by line of therapy and overall survival (OS). The real-world effectiveness of anti-PD-1/PD-L1 first-line therapy was also evaluated in patients with a NFE2L2 and/or KEAP1 mutation.
Of 703 patients included (median age: 70.0 years), 31.6% had a NFE2L2 and/or KEAP1 mutation. The most common first- and second-line treatments regardless of mutation status were platinum-based chemotherapies and anti-PD-1/PD-L1 therapies. The most common third-line treatment was anti-PD-1/PD-L1 therapy in patients with a NFE2L2 and/or KEAP1 mutation and single-agent chemotherapy in patients with wild-type disease. Patients with a NFE2L2 and/or KEAP1 mutation versus wild-type disease had significantly shorter rwPFS (4.54 vs. 6.25 months; P = .003) following first- but not second- or third-line therapy and shorter median OS (13.59 vs. 17.37 months; P = .4105). No survival differences were observed in patients with a NFE2L2 and/or KEAP1 mutation receiving first-line anti-PD-1/PD-L1 therapies versus other therapies.
Patients with advanced squamous cell NSCLC with a NFE2L2 and/or KEAP1 mutation have poor real-world survival, highlighting the need for a genotype-directed therapeutic strategy in this population.
NFE2L2和/或KEAP1突变与所有非小细胞肺癌（NSCLC）的预后较差相关。我们根据NFE2L2和KEAP1突变状态确定了晚期肺鳞状细胞癌患者的真实世界生存结局和治疗模式。
使用美国一个经过去识别化处理的临床基因组数据库进行了一项回顾性研究（2011年1月至2018年12月）。纳入研究期间有≥2次网络内就诊且进行了全面基因组分析的成年晚期肺鳞状细胞癌患者。结局包括按治疗线数划分的真实世界无进展生存期（rwPFS）和总生存期（OS）。还评估了NFE2L2和/或KEAP1突变患者中抗PD-1/PD-L1一线治疗的真实世界有效性。
在纳入的703例患者（中位年龄：70.0岁）中，31.6%有NFE2L2和/或KEAP1突变。无论突变状态如何，最常见的一线和二线治疗是铂类化疗和抗PD-1/PD-L1治疗。最常见的三线治疗是NFE2L2和/或KEAP1突变患者中的抗PD-1/PD-L1治疗以及野生型疾病患者中的单药化疗。与野生型疾病患者相比，NFE2L2和/或KEAP1突变患者在一线治疗后rwPFS显著更短（4.54个月对6.25个月；P = 0.003），但二线或三线治疗后无差异，中位OS也更短（13.59个月对17.37个月；P = 0.4105）。接受一线抗PD-1/PD-L1治疗的NFE2L2和/或KEAP1突变患者与接受其他治疗的患者之间未观察到生存差异。
患有NFE2L2和/或KEAP1突变的晚期肺鳞状细胞癌患者真实世界生存较差，突出了在该人群中采用基因型导向治疗策略的必要性。
