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Potential for afatinib as an optimal treatment for advanced non-small cell lung carcinoma in patients with uncommon EGFR mutations

2018; Elsevier BV; Volume: 127; Linguagem: Inglês

10.1016/j.lungcan.2018.11.018

1872-8332

Ichidai Tanaka, Masahiro Morise, Yuta Kodama, Akira Matsui, Naoya Ozawa, Sachiko Ozone, Daiki Goto, Ayako Miyazawa, Tetsunari Hase, Naozumi Hashimoto, Mitsuo Sato, Yoshinori Hasegawa,

PI3K/AKT/mTOR signaling in cancer

Uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are a heterogeneous group of genetic alterations that produce variable responses to EGFR-tyrosine kinase inhibitor (TKI) in patients with most of the evidence of the responses to EGFR-TKIs being based on small case studies or single case reports [ 1 Wu J.Y. Yu C.J. Chang Y.C. Yang C.H. Shih J.Y. Yang P.C. Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin. Cancer Res. 2011; 17: 3812-3821 Crossref PubMed Scopus (382) Google Scholar , 2 Lohinai Z. Hoda M.A. Fabian K. Ostoros G. Raso E. Barbai T. Timar J. Kovalszky I. Cserepes M. Rozsas A. Laszlo V. Grusch M. Berger W. Klepetko W. Moldvay J. Dome B. Hegedus B. Distinct epidemiology and clinical consequence of classic versus rare EGFR mutations in lung adenocarcinoma. J. Thorac. Oncol. 2015; 10: 738-746 Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar , 3 Galli G. Corrao G. Imbimbo M. Proto C. Signorelli D. Ganzinelli M. Zilembo N. Vitali M. de Braud F. Garassino M.C. Lo Russo G. Uncommon mutations in epidermal growth factor receptor and response to first and second generation tyrosine kinase inhibitors: a case series and literature review. Lung Cancer. 2018; 115: 135-142 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar ]. Several studies have demonstrated that patients with uncommon EGFR mutations respond poorly to first-generation EGFR-TKIs, such as gefitinib and erlotinib, compared to patients with common EGFR mutations [ 2 Lohinai Z. Hoda M.A. Fabian K. Ostoros G. Raso E. Barbai T. Timar J. Kovalszky I. Cserepes M. Rozsas A. Laszlo V. Grusch M. Berger W. Klepetko W. Moldvay J. Dome B. Hegedus B. Distinct epidemiology and clinical consequence of classic versus rare EGFR mutations in lung adenocarcinoma. J. Thorac. Oncol. 2015; 10: 738-746 Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar , 3 Galli G. Corrao G. Imbimbo M. Proto C. Signorelli D. Ganzinelli M. Zilembo N. Vitali M. de Braud F. Garassino M.C. Lo Russo G. Uncommon mutations in epidermal growth factor receptor and response to first and second generation tyrosine kinase inhibitors: a case series and literature review. Lung Cancer. 2018; 115: 135-142 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar , 4 Chen Y.M. Lai C.H. Chang H.C. Chao T.Y. Tseng C.C. Fang W.F. Wang C.C. Chung Y.H. Wang Y.H. Su M.C. Huang K.T. Chen H.C. Lin M.C. The impact of clinical parameters on progression-free survival of non-small cell lung cancer patients harboring EGFR-mutations receiving first-line EGFR-tyrosine kinase inhibitors. Lung Cancer. 2016; 93: 47-54 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar , 5 Klughammer B. Brugger W. Cappuzzo F. Ciuleanu T. Mok T. Reck M. Tan E.H. Delmar P. Klingelschmitt G. Yin A.Y. Spleiss O. Wu L. Shames D.S. Examining treatment outcomes with erlotinib in patients with advanced non-small cell lung cancer whose tumors harbor uncommon EGFR mutations. J. Thorac. Oncol. 2016; 11: 545-555 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ]. Among the rare subtypes, the two highest frequency mutations, G719X in exon18 and L861Q in exon21, have been recognized as being relatively sensitizing mutations; the objective overall response rate and the median progression-free survival (PFS) have been reported to be around 40–70% and 4.0–9.0 months, respectively [ [1] Wu J.Y. Yu C.J. Chang Y.C. Yang C.H. Shih J.Y. Yang P.C. Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin. Cancer Res. 2011; 17: 3812-3821 Crossref PubMed Scopus (382) Google Scholar , [6] Sutiman N. Tan S.W. Tan E.H. Lim W.T. Kanesvaran R. Ng Q.S. Jain A. Ang M.K. Tan W.L. Toh C.K. Chowbay B. EGFR mutation subtypes influence survival outcomes following first-line gefitinib therapy in advanced Asian NSCLC patients. J. Thorac. Oncol. 2017; 12: 529-538 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar , [7] O'Kane G.M. Bradbury P.A. Feld R. Leighl N.B. Liu G. Pisters K.M. Kamel-Reid S. Tsao M.S. Shepherd F.A. Uncommon EGFR mutations in advanced non-small cell lung cancer. Lung Cancer. 2017; 109: 137-144 Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar ]. Due to the similar efficiency obtained by platinum-doublet chemotherapy, the therapeutic strategy for advanced NSCLC patients with uncommon EGFR mutation has been inconsistent. Recently, a second-generation EGFR-TKI, afatinib, has shown superior efficacy over the first-generation EGFR-TKIs in NSCLC patients with common EGFR mutations [ [8] Park K. Tan E.H. O'Byrne K. Zhang L. Boyer M. Mok T. Hirsh V. Yang J.C. Lee K.H. Lu S. Shi Y. Kim S.W. Laskin J. Kim D.W. Arvis C.D. Kolbeck K. Laurie S.A. Tsai C.M. Shahidi M. Kim M. Massey D. Zazulina V. Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016; 17: 577-589 Abstract Full Text Full Text PDF PubMed Scopus (813) Google Scholar , [9] Paz-Ares L. Tan E.H. O'Byrne K. Zhang L. Hirsh V. Boyer M. Yang J.C. Mok T. Lee K.H. Lu S. Shi Y. Lee D.H. Laskin J. Kim D.W. Laurie S.A. Kolbeck K. Fan J. Dodd N. Marten A. Park K. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann. Oncol. 2017; 28: 270-277 Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar ]. Furthermore, a post-hoc analysis of the Lux-Lung -2, -3, and -6 trials showed that afatinib was active in NSCLC patients with uncommon EGFR mutations, and that the median PFS in the patients with G719X in exon 18 or L861Q in exon 21 were 13.8 months or 8.2 months, respectively [ [10] Yang J.C. Sequist L.V. Geater S.L. Tsai C.M. Mok T.S. Schuler M. Yamamoto N. Yu C.J. Ou S.H. Zhou C. Massey D. Zazulina V. Wu Y.L. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015; 16: 830-838 Abstract Full Text Full Text PDF PubMed Scopus (659) Google Scholar ]. These results indicate that afatinib could be an optimal treatment option for the patients with uncommon EGFR mutations. However, there have been no reports that show the superiority of afatinib over the first-generation EGFR-TKIs in a cohort study.