肺癌EGFR-TKI联合贝伐珠单抗治疗进展
Progress of EGFR-TKI Combined with Bevacizumab in the Treatment of Lung Cancer
DOI: 10.12677/ACM.2022.123258, PDF,    国家自然科学基金支持
作者: 谢志丹*, 梁亚奇：青海大学，青海 西宁；徐芹芹#：青海省人民医院，青海 西宁
关键词: 肺癌；阿贝伐珠单抗；EGFR-TKI；耐药；Lung Cancer； Bevacizumab； EGFR-TKI； Drug Resistance
摘要: 近年来肺癌发病率及死亡率均占癌症首位，其中约30%~40%的患者在确诊时存在EGFR突变，靶向药物的研发使这部分患者的治疗有了新的更精准的方向，多项实验证实EGFR-TKI (表皮生长因子受体酪氨酸激酶抑制剂)联合贝伐珠单抗(A + T)用药可显著延长此类患者的无进展生存期及5年生存率，但令人遗憾的是总生存期却没有明显获益，且均会面临耐药问题，随着分子生物学技术的深入探索，部分耐药机制已逐渐清晰，但A + T治疗依旧面临很多挑战，克服耐药刻不容缓。
Abstract: The incidence and mortality of lung cancer is still the highest in cancer patients worldwide. About 30%~40% of lung cancer patients were detected with EGFR mutation when they were first diagnosed. The development of target drugs provided a novel direction for precision therapy. Multiple clinical trials have confirmed the therapeutic efficiency of EGFR TKI combined with Bevacizumab (A + T) strategy which can significantly prolong progression-free survival and 5-year survival of the patients. However, there was no obvious benefit in overall survival of these patients because of the drug resistance. Even the mechanisms of lung cancer drug resistance have been clarified with the development of molecular biology techniques, the A + T therapeutic still faces many challenges. Thus it is urgent to develop a novel strategy to overcome its resistance.
文章引用：谢志丹, 梁亚奇, 徐芹芹. 肺癌EGFR-TKI联合贝伐珠单抗治疗进展[J]. 临床医学进展, 2022, 12(3): 1795-1800. https://doi.org/10.12677/ACM.2022.123258

参考文献

[1] Suster, D.I. and Mino-Kenudson, M. (2020) Molecular Pathology of Primary Non-Small Cell Lung Cancer. Archives of Medical Research, 51, 784-798. [Google Scholar] [CrossRef] [PubMed]
[2] 郑荣寿, 孙可欣, 张思维, 曾红梅, 邹小农, 陈茹, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28.
[3] Zhang, Y.L., Yuan, J.Q., Wang, K.F., Fu, X.H., Han, X.R., Threapleton, D., et al. (2016) The Prevalence of EGFR Mutation in Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Oncotarget, 7, 78985-78993. [Google Scholar] [CrossRef] [PubMed]
[4] Yano, S., Takeuchi, S., Nakagawa, T. and Yamada, T. (2012) Ligand-Triggered Resistance to Molecular Targeted Drugs in Lung Cancer: Roles of Hepatocyte Growth Factor and Epidermal Growth Factor Receptor Ligands. Cancer Science, 103, 1189-1194. [Google Scholar] [CrossRef] [PubMed]
[5] 王莉洁, 梁志欣, 喻航, 陈良安. 肺癌的驱动基因与靶向治疗研究进展[J]. 国际呼吸杂志, 2017, 37(4): 297-301.
[6] Gao, J., Li, H.R., Jin, C., Jiang, J.H. and Ding, J.Y. (2019) Strategies to Overcome Acquired Resistance to EGFR TKI in the Treatment of Non-Small Cell Lung Cancer. Clinical and Translational Oncology, 21, 1287-1301. [Google Scholar] [CrossRef] [PubMed]
[7] Wu, S.G. and Shih, J.Y. (2018) Management of Acquired Resistance to EGFR TKI-Targeted Therapy in Advanced Non-Small Cell Lung Cancer. Molecular Cancer, 17, Article No. 38. [Google Scholar] [CrossRef] [PubMed]
[8] Wang, Z., Zhou, P.U. and Li, G. (2016) Bevacizumab to Combat EGFR-TKI Resistance in a Patient with Advanced Non-Small Cell Lung Cancer Harboring an EGFR Mutation: A Case Report. Oncology Letters, 12, 356-360. [Google Scholar] [CrossRef] [PubMed]
[9] Yoshioka, H., Shimokawa, M., Seto, T., Morita, S., Yatabe, Y., Okamoto, I., et al. (2019) Final Overall Survival Results of WJTOG3405, a Randomized Phase III Trial Comparing Gefitinib versus Cisplatin with Docetaxel as the First-Line Treatment for Patients with Stage IIIB/IV or Postoperative Recurrent EGFR Mutation-Positive Non-Small-Cell Lung Cancer. Annals of Oncology, 30, 1978-1984. [Google Scholar] [CrossRef] [PubMed]
[10] Zhou, C., Wu, Y.L., Chen, G., Feng, J., Liu, X.Q., Wang, C., et al. (2015) Final Overall Survival Results from a Randomised, Phase III Study of Erlotinib versus Chemotherapy as First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer (OPTIMAL, CTONG-0802). Annals of Oncology, 26, 1877-1883. [Google Scholar] [CrossRef] [PubMed]
[11] Yang, J.C., Sequist, L.V., Zhou, C., Schuler, M., Geater, S.L., Mok, T., et al. (2016) Effect of Dose Adjustment on the Safety and Efficacy of Afatinib for EGFR Mutation-Positive Lung Adenocarcinoma: Post Hoc Analyses of the Randomized LUX-Lung 3 and 6 Trials. Annals of Oncology, 27, 2103-2110. [Google Scholar] [CrossRef] [PubMed]
[12] Mok, T.S., Cheng, Y., Zhou, X., Lee, K.H., Nakagawa, K., Niho, S., et al. (2021) Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs, 81, 257-266. [Google Scholar] [CrossRef] [PubMed]
[13] Tripathi, S.K., Pandey, K., Rengasamy, K.R.R. and Biswal, B.K. (2020) Recent Updates on the Resistance Mechanisms to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Resistance Reversion Strategies in Lung Cancer. Medicinal Research Reviews, 40, 2132-2176. [Google Scholar] [CrossRef] [PubMed]
[14] Ramalingam, S.S., Vansteenkiste, J., Planchard, D., Cho, B.C., Gray, J.E., Ohe, Y., et al. (2020) Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. New England Journal of Medicine, 382, 41-50. [Google Scholar] [CrossRef] 
[15] Wu, Y.L., Tsuboi, M., He, J., John, T., Grohe, C., Majem, M., et al. (2020) Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. New England Journal of Medicine, 383, 1711-1723. [Google Scholar] [CrossRef] 
[16] Leonetti, A., Sharma, S., Minari, R., Perego, P., Giovannetti, E. and Tiseo, M. (2019) Resistance Mechanisms to Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer. British Journal of Cancer, 121, 725-737. [Google Scholar] [CrossRef] [PubMed]
[17] Chikaishi, Y., Kanayama, M., Taira, A., Nabe, Y., Shinohara, S., Kuwata, T., et al. (2018) Effect of Erlotinib plus Bevacizumab on Brain Metastases in Patients with Non-Small Cell Lung Cancer. Annals of Translational Medicine, 6, 401. [Google Scholar] [CrossRef] [PubMed]
[18] Nagasaka, M., Zhu, V.W., Lim, S.M., Greco, M., Wu, F. And Ou, S.I. (2021) Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors for Advanced EGFR + NSCLC. Journal of Thoracic Oncology, 16, 740-763. [Google Scholar] [CrossRef] [PubMed]
[19] Yun, J., Lee, S.H., Kim, S.Y., Jeong, S.Y., Kim, J.H., Pyo, K.H. et al. (2020) Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discovery, 10, 1194-1209. [Google Scholar] [CrossRef] 
[20] 周振兴, 宋军民, 陈姬华, 吴强. 贝伐珠单抗在肿瘤治疗中的应用研究进展[J]. 药学进展, 2015, 39(7): 525-532.
[21] 徐萍, 李红梅. 贝伐珠单抗在非小细胞肺癌中的应用进展[J]. 中国肺癌杂志, 2017, 20(4): 272-277.
[22] Garcia, J., Hurwitz, H.I., Sandler, A.B., et al. (2020) Bevacizumabin Cancer Treatment: A Review of 15 Years of Clinical Experience and Future Outlook. Cancer Treatment Reviews, 86, Article ID: 102017. [Google Scholar] [CrossRef] [PubMed]
[23] Jiang, T., Li, A., Su, C., Li, X., Zhao, C., Ren, S., et al. (2017) Addition of Bevacizumab for Malignant Pleural Effusion as the Manifestation of Acquired EGFR-TKI Resistance in NSCLC Patients. Oncotarget, 8, 62648-62657. [Google Scholar] [CrossRef] [PubMed]
[24] Yamamoto, N., Seto, T., Nishio, M., Goto, K., Okamoto, I., Yamanaka, T., et al. (2018) Erlotinib plus Bevacizumab (EB) versus Erlotinib Alone (E) as First-Line Treatment for Advanced EGFR Mutation-Positive Non-Squamous Non-Small-Cell Lung Cancer (NSCLC): Survival Follow-Up Results of JO25567. Journal of Clinical Oncology, 36, 9007. [Google Scholar] [CrossRef] 
[25] Maemondo, M., Fukuhara, T., Saito, H., Furuya, N., Watanabe, K., Sugawara, S., et al. (2020) NEJ026: Final Overall Survivalanalysis of Bevacizumab plus Erlotinib Treatment for NSCLCpatients Harboringactivating EGFR-Mutations. Journal of Clinical Oncology, 38, 9506. [Google Scholar] [CrossRef] 
[26] Yamamoto, N., Seto, T., Nishio, M., Goto, K., Yamamoto, N., Okamoto, I., et al. (2021) Erlotinib plus Bevacizumab vs Erlotinib Monotherapy as First-Line Treatment for Advanced EGFR Mutation-Positive Non-Squamous Non-Small-Cell Lung Cancer: Survival Follow-up Results of the Randomized JO25567 Study. Lung Cancer, 151, 20-24. [Google Scholar] [CrossRef] [PubMed]
[27] Yu, H.A., Schoenfeld, A.J., Makhnin, A., Kim, R., Rizvi, H., Tsui, D., et al. (2020) Effect of Osimertinib and Bevacizumab on Progression-Free Survival for Patients with Metastatic EGFR-Mutant Lung Cancers: A Phase 1/2 Single-Group Open-Label Trial. JAMA Oncology, 6, 1048-1054. [Google Scholar] [CrossRef] [PubMed]
[28] Zhou, Q., Xu, C.R., Cheng, Y., Liu, Y.P., Chen, G.Y., Cui, J.W., et al. (2021) Bevacizumab plus Erlotinib in Chinese Patients with Untreated, EGFRmutated, Advanced NSCLC (ARTEMISCTONG1509): A Multicenter Phase 3 Study. Cancer Cell, 39, 1279-1291.E3. [Google Scholar] [CrossRef] [PubMed]
[29] Nakagawa, K., Garon, E.B., Seto, T., Nishio, M., Ponce Aix, S., Paz-Ares, L., et al. (2019) Ramucirumab plus Erlotinib in Patients with Untreated, EGFR-Mutated, Advanced Non-Small-Cell Lung Cancer (RELAY): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 20, 1655-1669. [Google Scholar] [CrossRef] 

为你推荐