Abstract 5462: Elevated creatine phosphokinase (CPK) as a strong predictor of aumolertinib (Au) treatment response in patients (pts) with advanced non-small cell lung cancer (NSCLC): post-hoc analysis of AENEAS

Abstract Background: In AENEAS trial (NCT03849768), first-line Au for EGFR-mutated, advanced NSCLC showed robust improvement in PFS over gefitinib (G). CPK elevation was the most common AE during Au treatment which may pose safety concerns. To evaluate the relationship between CPK elevation and Au efficacy, we performed a post-hoc analysis of AENEAS. Methods: AENEAS is a double-blind, randomized controlled phase III trial. Untreated advanced NSCLC pts with EGFR sensitizing mutations were assigned 1:1 to receive Au (110 mg QD) or G (250 mg QD). The primary endpoint was PFS. Secondary endpoints included ORR, DCR, DoR and DepOR. Data cutoff: Aug 1, 2021. Results: 37.9% (81/214) of pts receiving Au had CPK elevation, among whom the mPFS was 26.3 mos and was significantly longer (HR=0.45; 95% CI: 0.31-0.67; P<.0001) than that of the CPK-normal pts (133/214) at 13.9 mos. PFS benefits remained consistent across all prespecified subgroups. Also for all the secondary endpoints, CPK-elevated pts demonstrated significant benefits over CPK-normal pts (TABLE). Multivariable regression analysis revealed that CPK elevation was an independent predictor of prolonged PFS for pts receiving Au, with 54% reduced risk of progression or death for CPK-elevated pts compared with CPK-normal pts (HR=0.46; 95%CI: 0.31-0.68; P=.0001). Au demonstrated PFS benefits over G in both CPK-elevated pts (HR=0.40; 95% CI: 0.21-0.79; P=.0059) and CPK-normal pts (HR=0.63; 95% CI: 0.48-0.83; P=.0010), and the benefit was magnified in CPK-elevated pts. Further supported by post-hoc analysis of a phase 1/2 study (NCT02981108), PFS was also significantly prolonged in CPK-elevated pts receiving second or later line Au (17.7 vs 10.9 mos; HR=0.63; 95% CI: 0.46-0.87; P=.0049). Conclusion: Our study first revealed the predictive value of CPK elevation on improved treatment response of Au, which is of great significance to help guide medical care. Summary of Endpoints Elevated CPK(N=81) Normal CPK(N=133) PFS, months Median (95% CI) 26.3 (20.7-NA) 13.9 (12.4-19.8) HR (95% CI) 0.45 (0.31-0.67) P-value <0.0001 12-months PFS rate (95% CI) 84.9 (74.9-91.1) 59.4 (50.2-67.5) 24-months PFS rate (95% CI) 54.3 (42.4-64.7) 30.1 (21.9-38.8) DoR, months Median (95% CI) 23.5 (18.1-NA) 15.2 (10.2-19.2) HR (95% CI) 0.51 (0.33-0.79) P-value 0.0024 12-months DoR rate (95% CI) 77.7 (65.7-85.9) 55.8 (44.3-65.9) 24-months DoR rate (95% CI) 46.9 (33.7-59.0) 31.0 (20.9-41.6) ORR (95% CI), % 87.7 (78.5-93.9) 66.9 (58.2-74.8) OR (95% CI) 3.54 (1.64-7.64) P-value 0.0013 DCR (95% CI), % 98.8 (93.3-100.0) 89.5 (83.0-94.1) OR (95% CI) 9.59 (1.22-75.54) P-value 0.0318 DepOR, % Mean (Std) -50.5 (17.4) -42.0 (24.1) Range -100.0-3.6 -100.0-50.0 P-value 0.0105 Citation Format: Shun Lu, Chuan Li, Hong Jian, Xiaorong Dong, Jianhua Chen, Gongyan Chen, Yuping Sun, Yinghua Ji, Jiawei Wei, Si Sun, Zhenzhong Su, Qiu Sun, Hongying Wei, Qiong Wu. Elevated creatine phosphokinase (CPK) as a strong predictor of aumolertinib (Au) treatment response in patients (pts) with advanced non-small cell lung cancer (NSCLC): post-hoc analysis of AENEAS. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5462.