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

被引：48

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

来源：

ESMO OPEN | 2021年 / 6卷 / 06期

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.

引用

页数：13

共 106 条

[11] EGFR tyrosine kinase inhibitors beyond focal progression obtain a prolonged disease control in patients with advanced adenocarcinoma of the lung [J].

Conforti, Fabio ;

Catania, Chiara ;

Toffalorio, Francesca ;

Duca, Matteo ;

Spitaleri, Gianluca ;

Barberis, Massimo ;

Noberasco, Cristina ;

Delmonte, Angelo ;

Santarpia, Mariacarmela ;

Lazzari, Chiara ;

De Pas, Tommaso Martino .

LUNG CANCER, 2013, 81 (03) :440-444

[12] Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes [J].

Cortellini, A. ;

Leonetti, A. ;

Catino, A. ;

Pizzutillo, P. ;

Ricciuti, B. ;

De Giglio, A. ;

Chiari, R. ;

Bordi, P. ;

Santini, D. ;

Giusti, R. ;

De Tursi, M. ;

Brocco, D. ;

Zoratto, F. ;

Rastelli, F. ;

Citarella, F. ;

Russano, M. ;

Filetti, M. ;

Marchetti, P. ;

Berardi, R. ;

Torniai, M. ;

Cortinovis, D. ;

Sala, E. ;

Maggioni, C. ;

Follador, A. ;

Macerelli, M. ;

Nigro, O. ;

Tuzi, A. ;

Iacono, D. ;

Migliorino, M. R. ;

Banna, G. ;

Porzio, G. ;

Cannita, K. ;

Ferrara, M. G. ;

Bria, E. ;

Galetta, D. ;

Ficorella, C. ;

Tiseo, M. .

CLINICAL & TRANSLATIONAL ONCOLOGY, 2020, 22 (06) :844-851

[13] PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients [J].

D'Incecco, A. ;

Andreozzi, M. ;

Ludovini, V. ;

Rossi, E. ;

Capodanno, A. ;

Landi, L. ;

Tibaldi, C. ;

Minuti, G. ;

Salvini, J. ;

Coppi, E. ;

Chella, A. ;

Fontanini, G. ;

Filice, M. E. ;

Tornillo, L. ;

Incensati, R. M. ;

Sani, S. ;

Crino, L. ;

Terracciano, L. ;

Cappuzzo, F. .

BRITISH JOURNAL OF CANCER, 2015, 112 (01) :95-102

[14] Response to Dual Crizotinib and Osimertinib Treatment in a Lung Cancer Patient with MET Amplification Detected by Liquid Biopsy Who Acquired Secondary Resistance to EGFR Tyrosine Kinase Inhibition [J].

Deng, Lei ;

Kiedrowski, Lesli A. ;

Ravera, Elizabeth ;

Cheng, Haiying ;

Halmos, Balazs .

JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (09) :E169-E172

[15] Continuation of gefitinib plus chemotherapy prolongs progression-free survival in advanced non-small cell lung cancer patients who get acquired resistance to gefitinib without T790M mutations [J].

Ding, Ting ;

Zhou, Fei ;

Chen, Xiaoxia ;

Zhang, Shijia ;

Liu, Yinan ;

Sun, Hui ;

Ren, Shengxiang ;

Li, Xuefei ;

Zhao, Chao ;

Wang, Heyong ;

Zhou, Caicun .

JOURNAL OF THORACIC DISEASE, 2017, 9 (09) :2923-+

[16] Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach [J].

Engel, Julian ;

Richters, Andre ;

Getlik, Matthaeus ;

Tomassi, Stefano ;

Keul, Marina ;

Termathe, Martin ;

Lategahn, Jonas ;

Becker, Christian ;

Mayer-Wrangowski, Svenja ;

Gruetter, Christian ;

Uhlenbrock, Niklas ;

Kruell, Jasmin ;

Schaumann, Niklas ;

Eppmann, Simone ;

Kibies, Patrick ;

Hoffgaard, Franziska ;

Heil, Jochen ;

Menninger, Sascha ;

Ortiz-Cuaran, Sandra ;

Heuckmann, Johannes M. ;

Tinnefeld, Verena ;

Zahedi, Rene P. ;

Sos, Martin L. ;

Schultz-Fademrecht, Carsten ;

Thomas, Roman K. ;

Kast, Stefan M. ;

Rauh, Daniel .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (17) :6844-6863

[17] EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors [J].

Ercan, Dalia ;

Choi, Hwan Geun ;

Yun, Cai-Hong ;

Capelletti, Marzia ;

Xie, Ting ;

Eck, Michael J. ;

Gray, Nathanael S. ;

Jaenne, Pasi A. .

CLINICAL CANCER RESEARCH, 2015, 21 (17) :3913-3923

[18] Overcoming EGFRG724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors [J].

Fassunke, Jana ;

Mueller, Fabienne ;

Keul, Marina ;

Michels, Sebastian ;

Dammert, Marcel A. ;

Schmitt, Anna ;

Plenker, Dennis ;

Lategahn, Jonas ;

Heydt, Carina ;

Braegelmann, Johannes ;

Tumbrink, Hannah L. ;

Alber, Yannic ;

Klein, Sebastian ;

Heimsoeth, Alena ;

Dahmen, Ilona ;

Fischers, Rieke N. ;

Scheffler, Matthias ;

Ihle, Michaela A. ;

Priesner, Vanessa ;

Scheel, Andreas H. ;

Wagener, Svenja ;

Kron, Anna ;

Frank, Konrad ;

Garbert, Katia ;

Persigehl, Thorsten ;

Puesken, Michael ;

Haneder, Stefan ;

Schaaf, Bernhard ;

Rodermann, Ernst ;

Engel-Riedel, Walburga ;

Felip, Enriqueta ;

Smit, Egbert F. ;

Merkelbach-Bruse, Sabine ;

Reinhardt, H. Christian ;

Kast, Stefan M. ;

Wolf, Juergen ;

Rauh, Daniel ;

Buettner, Reinhard ;

Sos, Martin L. .

NATURE COMMUNICATIONS, 2018, 9

[19] Phase III study comparing bevacizumab plus erlotinib to erlotinib in patients with untreated NSCLC harboring activating EGFR mutations: NEJ026. [J].

Furuya, Naoki ;

Fukuhara, Tatsuro ;

Saito, Haruhiro ;

Watanabe, Kana ;

Sugawara, Shunichi ;

Iwasawa, Shunichiro ;

Tsunezuka, Yoshio ;

Yamaguchi, Ou ;

Okada, Morihito ;

Yoshimori, Kouzou ;

Nakachi, Ichiro ;

Gemma, Akihiko ;

Azuma, Koichi ;

Hagiwara, Koichi ;

Nukiwa, Toshihiro ;

Morita, Satoshi ;

Kobayashi, Kunihiko ;

Maemondo, Makoto .

JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)

[20] EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis [J].

Gainor, Justin F. ;

Shaw, Alice T. ;

Sequist, Lecia V. ;

Fu, Xiujun ;

Azzoli, Christopher G. ;

Piotrowska, Zofia ;

Huynh, Tiffany G. ;

Zhao, Ling ;

Fulton, Linnea ;

Schultz, Katherine R. ;

Howe, Emily ;

Farago, Anna F. ;

Sullivan, Ryan J. ;

Stone, James R. ;

Digumarthy, Subba ;

Moran, Teresa ;

Hata, Aaron N. ;

Yagi, Yukako ;

Yeap, Beow Y. ;

Engelman, Jeffrey A. ;

Mino-Kenudson, Mari .

CLINICAL CANCER RESEARCH, 2016, 22 (18) :4585-4593

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