Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies

被引:41
作者
Di Noia, V. [1 ]
D'Aveni, A. [2 ]
D'Argento, E. [3 ]
Rossi, S. [4 ]
Ghirardelli, P. [2 ]
Bortolotti, L. . [2 ]
Vavassori, V. [2 ]
Bria, E. [3 ,5 ]
Ceresoli, G. L. [2 ]
机构
[1] IRCCS Regina Elena Natl Canc Inst, Med Oncol 1 Unit, Via Elio Chianesi 53, I-00144 Rome, Italy
[2] Clin Humanitas Gavazzeni, Dept Med Oncol 1, Bergamo, Italy
[3] Fdn Policlin Univ Agostino Gemelli IRCCS, Comprehens Canc Ctr, Rome, Italy
[4] Humanitas Clin & Res Ctr, Dept Oncol & Hematol, Rozzano, Italy
[5] Univ Cattolica Sacro Cuore, Ist Med Interna & Geriatria, Rome, Italy
关键词
EGFR; osimertinib; non-small-cell lung cancer; tyrosine kinase inhibitors; progression; GEFITINIB PLUS CHEMOTHERAPY; TYROSINE KINASE INHIBITORS; OPEN-LABEL; 1ST-LINE TREATMENT; ACQUIRED-RESISTANCE; MEDIATES RESISTANCE; G724S MUTATION; ASIAN PATIENTS; ADVANCED NSCLC; PHASE-III;
D O I
10.1016/j.esmoop.2021.100280
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A precision medicine approach has been successfully applied in medical oncolog y for the treatment of non-small-cell lung cancer (NSCLC) through the identification of targetable driver molecular aberrations; activating mutations of epidermal growth factor receptor (EGFR) are the most common. Osimertinib, a third-generation, wild-type sparing, irreversible EGFR tyrosine kinase inhibitor (TKI), originally showed a striking activity after progression to first-and second-generation EGFR-TKIs when T790M resistance mutation was identified. Thereafter, upfront use of osimertinib became the standard of care based on overall survival benefit over first-generation TKIs erlotinib and gefitinib as reported in the FLAURA trial. For patients progressing on osimertinib, identification of resistance mechanisms is crucial to develop novel targeted therapeutic approaches. Moreover, innovative drugs or combination therapies are being developed for cases in which a specific resistance mechanism is not identifiable. In this review, the post-osimertinib treatment options for EGFR-mutated NSCLC are analyzed, with an outlook to ongoing clinical trials. An algorithm to guide clinicians in managing progression on osimertinib is proposed.
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页数:13
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