1.Afatinib in first-line setting for NSCLC harbouring common EGFR mutations: new light after the preliminary results of LUX-Lung 7?
Passaro A1, Pochesci A1, Spitaleri G1, Catania C1, Noberasco C1, Del Signore E1, de Marinis F1. J Thorac Dis. 2016 Mar;8(3):E217-20. doi: 10.21037/jtd.2016.02.21.
The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed dramatically the history of non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Several randomized prospective trials confirmed the superiority of these target agents about survival and response rate when comparing with platinum-based chemotherapy. Knowledge about EGFR mutations increased gradually during the development of target agents and different clinical trials. EGFR mutations cannot be considered all equal, but different entities should be considered in our clinical practice: exon 19 deletions, exon 21 mutation (L858R) and uncommon mutation (exon 20, exon 18 and double mutation). Nowadays, we dispose of three different EGFR TKIs (afatinib, erlotinib and gefitinib) approved for the treatment for first-line treatment of patients di NSCLC carrying EGFR, that was compared only by indirect analysis, producing data not always clear and convincing.
2.Tyrosine Kinase Inhibitors for the Elderly.
Hohenforst-Schmidt W1, Zarogoulidis P2, Steinheimer M1, Benhassen N1, Tsiouda T2, Baka S3, Yarmus L4, Stratakos G2, Organtzis J2, Pataka A2, Tsakiridis K5, Karapantzos I6, Karapantzou C6, Darwiche K7, Zissimopoulos A8, Pitsiou G2, Zarogoulidis K2, Man YG9 J Cancer. 2016 Mar 21;7(6):687-93. doi: 10.7150/jca.14819. eCollection 2016.
Until few years ago non-specific cytotoxic agents were considered the tip of the arrow as first line treatment for lung cancer. However; age > 75 was considered a major drawback for this kind of therapy. Few exceptions were made by doctors based on the performance status of the patient. The side effects of these agents are still severe for several patients. In the recent years further investigation of the cancer genome has led to targeted therapies. There have been numerous publications regarding novel agents such as; erlotinib, gefitinib and afatinib. In specific populations these agents have demonstrated higher efficiency and this observation is explained by the overexpression of the EGFR pathway in these populations. We suggest that TKIs should administered in the elderly, and with the word elderly we propose the age of 75. The treating medical doctor has to evaluate the performance status of a patient and decide the best treatment in several cases indifferent of the age.
3.Afatinib Is Active in Platinum-Refractory ERBB-Mutant Urothelial Carcinoma.
Cancer Discov. 2016 Apr 14. [Epub ahead of print]
HER2orERBB3alterations are predictive of afatinib response in refractory urothelial carcinomas.
4.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.
Park K1, Tan EH2, O'Byrne K3, Zhang L4, Boyer M5, Mok T6, Hirsh V7, Yang JC8, Lee KH9, Lu S10, Shi Y11, Kim SW12, Laskin J13, Kim DW14, Arvis CD15, Kölbeck K16, Laurie SA17, Tsai CM18, Shahidi M19, Kim M20, Massey D19, Zazulina V19, Paz-Ares L21. Lancet Oncol. 2016 Apr 12. pii: S1470-2045(16)30033-X. doi: 10.1016/S1470-2045(16)30033-X. [Epub ahead of print]
BACKGROUND: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting.