Author/Editor		Peters, Solange; Curioni-Fontecedro, Alessandra; Nechushtan, Hovav; Shih, Jin-Yuan; Liao, Wei-Yu; Gautschi, Oliver; Spataro, Vito J.; Unk, Mojca; Lorence, Robert M.; Cseh, Agnieszka
Title		Activity of afatinib in heavily pretreated patients with HER2 mutation-positive advanced NSCLC
Type		članek
Vol. and No.		Letnik 13, št. 12
Publication year		2018
Volume		str. 1897-1905
ISSN		1556-0864 - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Language		eng
Abstract		Approximately 1%4% of non-small-cell lung cancer (NSCLC) tumors harbor a human epidermal growth factor receptor 2 (HER2) mutation; there is no approved targeted treatment for this subgroup. Methods: Patients with stage IV NSCLC that progressed after clinical benefit on erlotinib/gefitinib and/or had activating epidermal growth factor receptor (EGFR) or HER2 mutations, had exhausted other treatments, and were ineligible for afatinib trials, were enrolled in a named patient use (NPU) program, receiving afatinib 30%50 mg/day on a compassionate basis within routine clinical practice. Efficacy and safety were retrospectively assessed in the subgroup with HER2 mutation-positive NSCLC. Results: Twenty-eight heavily pretreated patients in the NPU program had a documented HER2 mutation by local testing. Median time-to-treatment failure (TTF; time from treatment initiation to discontinuation for any reason) was 2.9 months; eight patients (29%) had TTF > 1 year. Objective response rate (ORR) was 19% (3/16 patients with response data achieved partial response) and disease control rate (DCR) was 69% (11/16). Among 12 patients for whom type of HER2 mutation was specified, ten had a p.A775_G776insYVMA insertion in exon 20, four of whom (40%) remained on afatinib > 1 year. This subgroup had median TTF of 9.6 months, ORR 33% (2/6), and DCR 100% (6/6). Conclusions: This analysis of patients treated in clinical practice provides further evidence of the activity of afatinib in HER2 mutation-positive NSCLC, and suggests that identification of specific subgroups with certain mutations, such as p.A775_G776ins/YVMA insertion in exon 20, could help optimize outcomes with HER2-targeted treatment.
Keywords		nedrobnocelični rak rak pljuč HER2 mutacije kemoterapija adenokarcinom non-small-cell lung cancer lung cancer HER2 mutations chemotherapy