*仅供医学专业人士阅读参考 罕见突变也有“特效药”了 EGFR突变是中国肺腺癌人群最常检出的可靶向驱动基因变异。近年来,随着对肿瘤分子生物学研究的不断深入,临床研究者对EGFR突变患者进一步细分。EGFR突变常发生在18-21号外显子,最常见的突变类型为19号外显子缺失突变和21号外显子L858R点突变,可达到80%以上。除此之外最常见的便是EGFR 20号外显子插入突变(EGFR exon 20ins),约占总体EGFR突变肺腺癌人群的6%,与经典突变患者的临床特征类似,常发生于女性、不吸烟的肺腺癌患者中[1-3]。 然而,不同于常见突变患者对酪氨酸激酶抑制剂(TKI)敏感,EGFR exon 20ins患者对早期TKI表现为原发耐药,对一代TKI吉非替尼/厄洛替尼的客观缓解率(ORR)为0%,对二代TKI阿法替尼的ORR为11%,中位无进展生存期(PFS)小于2个月[4]。不过有研究显示,三代TKI奥希替尼对EGFR exon 20ins有一定的效果,ORR为25%,中位PFS为9.7个月[5]。 参考文献: [1]Sabari JK,Heymach JV,Sandy B.Hitting the Right Spot:Advances in the Treatment of NSCLC With Uncommon EGFR Mutations.J Natl Compr Canc Netw.2021;19(Suppl_2):S1-S11.doi:10.6004/jnccn.2021.0200. [2]Oxnard GR,Lo PC,Nishino M,et al.Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions.J Thorac Oncol.2013;8(2):179-84.doi:10.1097/JTO.0b013e3182779d18. [3]Kobayashi Y,Mitsudomi T.Not all epidermal growth factor receptor mutations in lung cancer are created equal:Perspectives for individualized treatment strategy.Cancer Sci.2016;107(9):1179-86.doi:10.1111/cas.12996. [4]Robichaux JP,Elamin YY,Tan Z,et al.Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer.Nat Med.2018;24(5):638-646.doi:10.1038/s41591-018-0007-9. [5]Piotrowska Z,Wang Y,Sequist LV,et al.ECOG-ACRIN 5162:a phase II study of osimertinib 160 mg in NSCLC with EGFR exon 20 insertions[abstract].J Clin Oncol 2020;38(Suppl):Abstract 9513. [6]Wang J,Wang B,Chu H,Yao Y.Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer with activating EGFR mutations.Onco Targets Ther.2016;9:3711-26.doi:10.2147/OTT.S106399. [7]Robichaux JP,Elamin YY,Tan Z,et al.Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer.Nat Med.2018;24(5):638-646.doi:10.1038/s41591-018-0007-9. [8]Vasconcelos PENS,Kobayashi IS,Kobayashi SS,Costa DB.Preclinical characterization of mobocertinib highlights the putative therapeutic window of this novel EGFR inhibitor to EGFR exon 20 insertion mutations.JTO Clin Res Rep.2021;2(3):100105.doi:10.1016/j.jtocrr.2020.100105. [9]NCCN Guidelines Version 1.2022 Non-Small Cell Lung Cancer. [10]Yun J,Lee SH,Kim SY,et al.Antitumor Activity of Amivantamab(JNJ-61186372),an EGFR-MET Bispecific Antibody,in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC.Cancer Discov.2020;10(8):1194-1209.doi:10.1158/2159-8290.CD-20-0116. [11]Vijayaraghavan S,Lipfert L,Chevalier K,et al.Amivantamab(JNJ-61186372),an Fc Enhanced EGFR/cMet Bispecific Antibody,Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis.Mol Cancer Ther.2020;19(10):2044-2056.doi:10.1158/1535-7163. [12]Sabari JK et al.,Amivantamab in post-platinum EGFR exon 20 insertion mutation non-small cell lung cancer.J Thorac Oncol 2021;16(3):S108-S109. [13]Doebele X,Riely GJ,Spira K,et al.First report of safety,PK,and preliminary antitumor activity of the oral EGFR/HER2 exon 20 inhibitor TAK-788(AP32788)in non-small cell lung cancer[abstract].J Clin Oncol 2018;36(Suppl):Abstract 9015. [14]Neal J et al.,Safety,PK,and preliminary antitumor activity of the oral EGFR/HER2 exon 20 inhibitor TAK-788 in NSCLC.J Thorac Oncol 2018;13(10):S599. [15]Janne PA,Neal JW,Camidge DR,et al.Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions[abstract].J Clin Oncol 2019;37(Suppl):Abstract 9007. [16]Zhou C,Ramalingam S,Li B,et al.Mobocertinib in NSCLC with EGFR exon 20 insertions:results from the EXCLAIM and pooled platinum-pretreated patient populations.J Thorac Oncol2021;16:S108. [17]Le X,Goldman JW,Clarke JM,et al.Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients[abstract].J Clin Oncol 2020;38(Suppl):Abstract 9514. |
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