Jiang Yu, Su Zixuan, Lin Yuechun, Xiong Yaming, Li Caichen, Li Jianfu, Wang Runchen, Zhong Ran, Cheng Bo, He Jianxing, Xie Zhanhong, Liang Wenhua
Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Respiratory Disease, Guangzhou, China.
Transl Lung Cancer Res. 2021 Sep;10(9):3771-3781. doi: 10.21037/tlcr-21-600.
The use of tyrosine kinase inhibitors (TKIs) is associated with incident creatine kinase (CK) elevation in the treatment of advanced non-small cell lung cancer (NSCLC) patients. However, whether higher CK levels are associated with better antitumor responses or survival remains to be explored. We intend to investigate the clinical correlation between CK levels and TKI efficacy in advanced NSCLC.
In this retrospective study, we enrolled 135 patients with stage IV NSCLC receiving TKI-based therapy in our center between June 2012 to July 2020. CK levels were monitored from the initiation of TKI medication and during the administration period. An X-tile analysis provided the optimal cutoff point for higher baseline CK. Patients were identified and grouped according to their baseline CK level and fold changes during TKI therapy. The primary endpoints included progression-free survival (PFS) and overall survival (OS), and the objective response rate (ORR) was calculated as the secondary endpoint.
Among the 135 patients included in our study, those with higher baseline CK levels (≥70 U/L) had favorable PFS (15.2 8.8 months; P=0.028), while patients with significantly elevated CK (the highest CK value/baseline CK value ≥2 times) appeared to gain better PFS (14.6 10.0 months; P=0.139). The overall ORR was 67.4%. Patients with higher baseline CK levels had numerically higher ORR (74.6% 60.3%; P=0.076). Similarly, patients with significant CK elevation had a superior 4-month PFS rate (77.6% 59.7%; P=0.029). Results from the subgroup analyses were identical to the overall ones. For patients with higher baseline CK levels, those experiencing significant CK elevation had prolonged PFS (17.2 14.2 months; P=0.038); a same trend was obtained from the lower baseline CK group (<70 U/L) (9.4 7.9 months; P=0.038). In multivariable analysis, higher baseline CK level and significant CK elevation remained statistically associated with PFS, with hazard ratios of 0.48 and 0.59, respectively.
Both higher baseline CK levels and significant CK elevation after treatment were correlated with prolonged PFS in NSCLC treated with TKIs, suggesting the potential prognostic and predictive impact of CK level on these patients.
在晚期非小细胞肺癌（NSCLC）患者的治疗中，使用酪氨酸激酶抑制剂（TKIs）与肌酸激酶（CK）升高有关。然而，较高的CK水平是否与更好的抗肿瘤反应或生存率相关仍有待探索。我们旨在研究晚期NSCLC患者CK水平与TKI疗效之间的临床相关性。
在这项回顾性研究中，我们纳入了2012年6月至2020年7月期间在本中心接受基于TKI治疗的135例IV期NSCLC患者。从开始使用TKI药物时及给药期间监测CK水平。X-tile分析提供了较高基线CK的最佳截断点。根据患者的基线CK水平和TKI治疗期间的变化倍数进行识别和分组。主要终点包括无进展生存期（PFS）和总生存期（OS），客观缓解率（ORR）作为次要终点进行计算。
在我们纳入研究的135例患者中，基线CK水平较高（≥70 U/L）的患者具有良好的PFS（15.2±8.8个月；P=0.028），而CK显著升高（最高CK值/基线CK值≥2倍）的患者似乎获得了更好的PFS（14.6±10.0个月；P=0.139）。总体ORR为67.4%。基线CK水平较高的患者ORR在数值上更高（74.6%对60.3%；P=0.076）。同样，CK显著升高的患者4个月PFS率更高（77.6%对59.7%；P=0.029）。亚组分析结果与总体结果一致。对于基线CK水平较高的患者，CK显著升高的患者PFS延长（17.2±14.2个月；P=0.038）；在基线CK水平较低（<70 U/L）的组中也获得了相同的趋势（9.4±7.9个月；P=0.038）。在多变量分析中，较高的基线CK水平和CK显著升高与PFS仍具有统计学相关性，风险比分别为0.48和0.59。
较高的基线CK水平和治疗后CK显著升高均与接受TKIs治疗的NSCLC患者的PFS延长相关，提示CK水平对这些患者具有潜在的预后和预测影响。
