Efficacy and Safety of Arotinib Combined with Ektinib in Patients with Stage ⅢB/ Ⅳ EGFR Gene Mutant Non-small Cell Lung Cancer
JIANG Zhou, CHEN Jian-hua
Department of Thoracic Medicine,Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Hunan Cancer Hospital,Changsha Hunan 410031
Abstract 【Objective】 To investigate the efficacy and safety of Arotinib combined with Ektinib in the treatment of non-small cell lung cancer (NSCLC) patients with stage ⅢB/Ⅳ human epidermal growth factor receptor (EGFR) gene mutations. 【Methods】A total of 27 patients with stage ⅢB/Ⅳ EGFR mutant NSCLC initially treated in our hospital from March 2019 to March 2021 were randomly divided into the observation group (treated with Arotinib combined with Ektinib) and the control group (treated with Ektinib). The efficacy, progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the two groups were compared. 【Results】Up to March 2022, the median PFS in the observation group was 15.50 months, significantly longer than 10.00 months in the control group, and the difference was statistically significant. According to different mutation types, they were divided into 19 exon deletion L858R point mutation group and 21 exon deletion L858R point mutation group. The median PFS of patients with 19 exon deletion L858R point mutation group in the observation group was 16.00 months, significantly higher than that of patients with 19 exon deletion L858R point mutation group in the control group for 11.75 months, and the difference was statistically significant (P<0.05); The median PFS of patients with exon 21 deletion L858R point mutation in the observation group was 14.00 months, compared with 8.50 months in patients with exon 21 deletion L858R point mutation in the control group, the difference was not statistically significant (P>0.05); After 6 weeks of treatment, the ORR and DCR of the observation group were 75.00% (9/12) and 91.67% (11/12), respectively, compared with 53.33% (8/15) and 80.00% (12/15) of the control group, the difference was not statistically significant (P>0.05). The proportion of hypertension and gingival bleeding in the observation group was higher, in which 2 cases of hypertension and transaminase increased by 3 levels, and all of them decreased to 1 level after symptomatic treatment with drugs; The incidence of skin rash, skin pruritus and paronychia in the control group was slightly higher than that in the observation group. The incidence of skin rash, skin pruritus, paronychia and transaminase increased by 3 levels. After symptomatic treatment, they all improved and can continue to be treated. The toxic and side effects of the two groups of patients were controllable as a whole. 【Conclusion】 Arotinib combined with Ektinib can significantly improve PFS in patients with stage ⅢB/Ⅳ NSCLC, and the safety is good.
[1] FRIEDLAENDER A,SUBBIAH V,RUSSO A,et al. EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment[J]. Nat Rev Clin Oncol,2022,19(1):51-69.
[2] COOPER A J,SEQUIST L V,LIN J J.Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management[J].Nat Rev Clin Oncol,2022,21:43-53.
[3] ZHOU Q,XU C R,CHENG Y. Bevacizumab plus erlotinib in Chinese patients with untreated,EGFR-mutated,advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study[J].Cancer Cell,2021,39(9):1279-1293.
[4] FREITES-MARTINEZ A,SANTANA N,ARIAS-SANTIAGO S,et al. Using the common terminology criteria for adverse events (CTCAE-Version 5.0) to evaluate the severity of adverse events of anticancer therapies[J].Actas Dermosifiliogr (Engl Ed),2021,112(1):90-112.
[5] TAN A C,TAN D S W. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations[J].J Clin Oncol,2022,40(6):611-625.
[6] SHI Y K,WANG L,HAN B H,et al.First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3,open-label,randomized study[J].Ann Oncol,2017,28(10):2443-2450.
[7] PETRELLI F,BORGONOVO K,CABIDDU M,et al. Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small-cell lung cancer: a meta-analysis of 13 randomized trials[J].Clin Lung Cancer,2012,13(2):107-142.
[8] HOWE O,WHITE L,CULLEN D,et al.A 4-Gene signature of CDKN1,FDXR,SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity[J].Int J Mol Sci,2021,22(9):1245-1267.
[9] GAMERITH G,KOCHER F,RUDZKI J,et al. ASCO 2018 NSCLC highlights-combination therapy is key[J].Memo,2018,11(4):266-271.
[10] LU J.Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy[J].Eur Respir J,2019,53(3): 1121-1134.
[11] HAN B,LI K,WANG Q,et al.Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the alter 0303 phase 3 randomized clinical trial[J].JAMA Oncol,2018,4(11):1569-1575.
[12] SHEN G S,ZHENG F C,REN D F,et al. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development[J].J Hematol Oncol,2018,11(1):120-132.
[13] SAITO H. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label,randomised,multicentre,phase 3 trial[J].Lancet Oncol,2019,20(5):625-635.
[14] WEI X X,CHEN Y H,JIANG X J,et al. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments[J].Mol Cancer,2021,20(1):7-15.
2022, Vol. 39 
