埃克替尼联合化疗在有EGFR敏感突变的初治非小细胞肺癌患者中的回顾性分析
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摘要
目的本研究分析在有表皮生长因子受体(EGFR)突变的初治非小细胞肺癌(NSCLC)患者中埃克替尼与埃克替尼联合化疗或单独化疗的疗效,并分析实际中,不同的基因突变(EGFR外显子19缺失)和L858R突变在不同治疗方法中的疗效。方法在2015年1月-2017年12月的回顾性分析中研究了191例患者。分析了患者的基线特征、疗效及不良事件。主要终点为无进展生存期(PFS)。结果联合治疗组的PFS较长,总生存期(OS)和客观缓解率(ORR)均优于埃克替尼组或化疗组。对于EGFR 19外显子缺失的患者,联合组的PFS、OS和ORR优于埃克替尼或化疗组。对于EGFR L858R突变的患者,联合组PFS和ORR较好,但OS没有明显延长。3级或4级不良事件最常见于联合治疗组或单独化疗组。未发生与药物有关的间质性肺病或与药物有关的死亡。结论埃克替尼与化疗联合应用于有敏感EGFR突变的初治非小细胞肺癌患者,可改善PFS和OS,尤其是那些具有EGFR外显子19缺失的患者。
Objective To investigate and analyze effects of icotinib combined chemotherapy on untreated non small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)sensitive gene mutations,and effects of different treatments on different gene mutations(the deletion of EGFR exon 19 and L858Rmutation)in practice.Methods A total of 191 patients were studied in the retrospective analysis from January 2015 to December 2017.The baseline characteristics,efficacy and adverse events were analyzed.The main end point was progression free survival(PFS).Results The combination group had longer PFS,a better overall response rate(OS)and a better objective response rate(ORR)than those of either icotinib or chemotherapy.For patients with EGFR exon 19 deletion,PFS,OS and ORR in the combination group were better than those in icotinib or chemotherapy group.For patients with EGFR L858 R mutation,PFS and ORR were better in the combined group,but OS was not significantly prolonged.The most common reports of grade 3or 4adverse events were in the combination therapy or chemotherapy alone.No drug-related interstitial lung disease or drug-related deaths occurred.Conclusion Icotinib combined with chemotherapy in patients with untreated NSCLC with sensitive EGFR mutations can improve PFS and OS,especially in those with EGFR exon 19 deletion.
Objective To investigate and analyze effects of icotinib combined chemotherapy on untreated non small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)sensitive gene mutations,and effects of different treatments on different gene mutations(the deletion of EGFR exon 19 and L858Rmutation)in practice.Methods A total of 191 patients were studied in the retrospective analysis from January 2015 to December 2017.The baseline characteristics,efficacy and adverse events were analyzed.The main end point was progression free survival(PFS).Results The combination group had longer PFS,a better overall response rate(OS)and a better objective response rate(ORR)than those of either icotinib or chemotherapy.For patients with EGFR exon 19 deletion,PFS,OS and ORR in the combination group were better than those in icotinib or chemotherapy group.For patients with EGFR L858 R mutation,PFS and ORR were better in the combined group,but OS was not significantly prolonged.The most common reports of grade 3or 4adverse events were in the combination therapy or chemotherapy alone.No drug-related interstitial lung disease or drug-related deaths occurred.Conclusion Icotinib combined with chemotherapy in patients with untreated NSCLC with sensitive EGFR mutations can improve PFS and OS,especially in those with EGFR exon 19 deletion.
引文
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[2]吕丽英,王留兴,周学良,等.盐酸埃克替尼加倍用量和化疗对靶向治疗后进展的晚期肺腺癌的临床疗效和安全性比较[J].中国实用医刊,2018,45(4):29-31.
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[5]ZWITTER M,RAJER M,STANIC K,et al.Intercalated chemotherapy and erlotinib for non-small cell lung cancer(NSCLC)with activating epidermal growth factor receptor(EGFR)mutations[J].Cancer Biol Ther,2016,17(8):833-839.
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[7]ENGEL J,RICHTERS A,GETLIK M,et al.Targeting drug resistance in EGFR with covalent inhibitors:a structure-based design approach[J].J Med Chem,2015,58(17):6844-6863.
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[9]WANG S,CANG S,LIU D.Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer[J].J Hematol Oncol,2016(9):34.
[10]WANG S,TSUI S T,LIU C,et al.EGFR C797Smutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer[J].J Hematol Oncol,2016,9(1):59.
[11]CHENG Y,MURAKAMI H,YANG P C,et al.Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous nonsmall-cell lung cancer with activating epidermal growth factor receptor mutations[J].J Clin Oncol,2016,34(27):3258-3266.
[12]潘伟佳,朱奕鸣,钟华芳,等.埃克替尼与吉非替尼在一线治疗晚期EGFR阳性肺腺癌患者中的疗效分析[J].中国实用医刊,2018,45(11):105-106.
[13]刘舒婷,赵大海.晚期非小细胞肺癌患者靶向药物(埃克替尼)耐药后再选择的分析[J].临床肺科杂志,2018,23(3):406-410.
[2]吕丽英,王留兴,周学良,等.盐酸埃克替尼加倍用量和化疗对靶向治疗后进展的晚期肺腺癌的临床疗效和安全性比较[J].中国实用医刊,2018,45(4):29-31.
[3]MITSUDOMI T,MORITA S,YATABE Y,et al.West Japan Oncology Group gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor(WJTOG3405):an open label,randomised phase 3trial[J].Lancet Oncol,2010,11(2):121-128.
[4]丛日楠,谷芳,王冰.吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因敏感突变晚期NSCLC患者的疗效观察[J].现代肿瘤医学,2018,26(2):216-219.
[5]ZWITTER M,RAJER M,STANIC K,et al.Intercalated chemotherapy and erlotinib for non-small cell lung cancer(NSCLC)with activating epidermal growth factor receptor(EGFR)mutations[J].Cancer Biol Ther,2016,17(8):833-839.
[6]NIU F Y,WU Y L.Novel agents and strategies for overcoming EGFR-TKIs resistance[J].Exp Hematol Oncol,2014,3(1):2.
[7]ENGEL J,RICHTERS A,GETLIK M,et al.Targeting drug resistance in EGFR with covalent inhibitors:a structure-based design approach[J].J Med Chem,2015,58(17):6844-6863.
[8]WANG S,SONG Y,YAN F,et al.Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors[J].Front Med,2016,10(4):383-388.
[9]WANG S,CANG S,LIU D.Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer[J].J Hematol Oncol,2016(9):34.
[10]WANG S,TSUI S T,LIU C,et al.EGFR C797Smutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer[J].J Hematol Oncol,2016,9(1):59.
[11]CHENG Y,MURAKAMI H,YANG P C,et al.Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous nonsmall-cell lung cancer with activating epidermal growth factor receptor mutations[J].J Clin Oncol,2016,34(27):3258-3266.
[12]潘伟佳,朱奕鸣,钟华芳,等.埃克替尼与吉非替尼在一线治疗晚期EGFR阳性肺腺癌患者中的疗效分析[J].中国实用医刊,2018,45(11):105-106.
[13]刘舒婷,赵大海.晚期非小细胞肺癌患者靶向药物(埃克替尼)耐药后再选择的分析[J].临床肺科杂志,2018,23(3):406-410.