Federico Cappuzzo1, Giovanna Finocchiaro, Francesco Grossi, Paolo Bidoli, Adolfo Favaretto, Antonio Marchetti, Maria Luisa Valente, Agnieszka Cseh, Laura Clementi, Dan Massey, Armando Santoro. 1. *Istituto Toscano Tumori, Ospedale Civile di Livorno, Livorno, Italy; †Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS, Rozzano, Italy; ‡IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Lung Cancer Unit, Genova, Italy; §San Gerardo Hospital, Monza, Italy; ‖Istituto Oncologico Veneto IRCSS, Padova, Italy; ¶Clinical Research Center, Center of Excellence on Aging, University Foundation, Chieti, Italy; #IRCCS Humanitas Clinical Institute, Rozzano, Milan, Italy; **Boehringer Ingelheim Pharma GmbH & Co. KG, Vienna, Austria; ††Boehringer Ingelheim Italia SpA, Milan, Italy; and ‡‡Boehringer Ingelheim Ltd., Bracknell, UK.
Abstract
INTRODUCTION:Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. This phase II study investigated the activity and safety of afatinib in advanced non-small-cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation. METHODS:EGFR gene overexpression was assessed by FISH analysis; patients with high polysomy or gene amplification were considered FISH positive. Patients received daily afatinib less than or equal to 50 mg (monotherapy). Endpoints included objective response rate (ORR; primary), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Of 223 patients screened, 69 patients were FISH-positive and met eligibility criteria for treatment. The ORR was 13.0% overall (n =9 of 69). Higher ORRs were observed in patients with gene amplification (20.0%; n =5 of 25) and EGFR mutation-positive tumors (25.0%; n =3 of 12). The DCR was 50.7% overall (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR mutation-positive tumors 66.7% (n = 8 of 12). In the overall population, median PFS was 8.4 weeks and median OS was 50.4 weeks. The most common afatinib-related adverse events were rash/acne (83%) and diarrhea (78%). CONCLUSIONS:First- or second-line afatinib demonstrated preliminary activity and manageable safety in EGFR FISH-positive patients with advanced non-small-cell lung cancer.
RCT Entities:
INTRODUCTION:Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. This phase II study investigated the activity and safety of afatinib in advanced non-small-cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation. METHODS:EGFR gene overexpression was assessed by FISH analysis; patients with high polysomy or gene amplification were considered FISH positive. Patients received daily afatinib less than or equal to 50 mg (monotherapy). Endpoints included objective response rate (ORR; primary), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Of 223 patients screened, 69 patients were FISH-positive and met eligibility criteria for treatment. The ORR was 13.0% overall (n =9 of 69). Higher ORRs were observed in patients with gene amplification (20.0%; n =5 of 25) and EGFR mutation-positive tumors (25.0%; n =3 of 12). The DCR was 50.7% overall (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR mutation-positive tumors 66.7% (n = 8 of 12). In the overall population, median PFS was 8.4 weeks and median OS was 50.4 weeks. The most common afatinib-related adverse events were rash/acne (83%) and diarrhea (78%). CONCLUSIONS: First- or second-line afatinib demonstrated preliminary activity and manageable safety in EGFR FISH-positive patients with advanced non-small-cell lung cancer.
Authors: Carlo Genova; Mark A Socinski; Rebecca R Hozak; Gu Mi; Raffael Kurek; Javad Shahidi; Luis Paz-Ares; Nick Thatcher; Christopher J Rivard; Marileila Varella-Garcia; Fred R Hirsch Journal: J Thorac Oncol Date: 2017-11-20 Impact factor: 15.609
Authors: Xinfang Mao; Zhenghu Chen; Yanling Zhao; Yang Yu; Shan Guan; Sarah E Woodfield; Sanjeev A Vasudevan; Ling Tao; Jonathan C Pang; Jiaxiong Lu; Huiyuan Zhang; Fuchun Zhang; Jianhua Yang Journal: Oncotarget Date: 2017-01-03
Authors: Ewa Szutowicz-Zielińska; Krzysztof Konopa; Anna Kowalczyk; Małgorzata Suszko-Każarnowicz; Renata Duchnowska; Aleksandra Szczęsna; Magdalena Ratajska; Aleksander Sowa; Janusz Limon; Wojciech Biernat; Tomasz Burzykowski; Jacek Jassem; Rafał Dziadziuszko Journal: Oncotarget Date: 2017-03-07