PMID- 25682316 OWN - NLM STAT- MEDLINE DCOM- 20151201 LR - 20190221 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 88 IP - 1 DP - 2015 Apr TI - Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma. PG - 63-9 LID - S0169-5002(15)00074-4 [pii] LID - 10.1016/j.lungcan.2015.01.013 [doi] AB - OBJECTIVES: Afatinib, an oral irreversible ErbB family blocker, has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. Other potential biomarkers predicting response to afatinib, such as human epidermal growth factor receptor-2 (HER2) mutations and EGFR gene amplification, have not been validated yet. This phase II study investigated whether afatinib conferred clinical benefit in cohorts of adenocarcinoma patients with: (1) EGFR mutation and failing on erlotinib/gefitinib; or (2) increased copy number of EGFR by fluorescence in situ hybridization (FISH); or (3) HER2 mutation. MATERIALS AND METHODS: Patients started daily afatinib 50mg monotherapy. Upon disease progression, patients could continue, at the investigator's discretion, afatinib (40mg) with the addition of paclitaxel (80mg/m(2) weekly for 3 weeks/4-week cycle). Endpoints included confirmed objective response (OR), progression-free survival (PFS), disease control, and safety. RESULTS: Of 41 patients treated (cohort 1: n=32; cohort 2: n=2; cohort 3: n=7), 33 received afatinib monotherapy; eight subsequently received afatinib plus paclitaxel. With afatinib monotherapy, one patient achieved a confirmed OR (partial response [PR]; cohort 2). Two further patients achieved unconfirmed PRs (one each in cohort 1 and cohort 3). Disease control was achieved by 17/32 (53%), 2/2 (100%) and 5/7 (71%) patients in cohorts 1, 2 and 3, respectively. In patients receiving combination therapy (median PFS: 6.7 weeks), one (cohort 3) had confirmed PR of 41.9 weeks. The most common afatinib-related adverse events were diarrhea (95%) and rash/acne (80%). CONCLUSION: Afatinib demonstrated signs of clinical activity in heavily pretreated patients with activating HER2 or EGFR mutations or EGFR FISH-positive tumors. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - De Greve, Jacques AU - De Greve J AD - Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: jacques.degreve@uzbrussel.be. FAU - Moran, Teresa AU - Moran T AD - Institut Catala d'Oncologia, Hospital Germans Trias I Pujol, Universitat Autonoma de Barcelona, Departament de Medicina, Badalona, Spain. Electronic address: mmoran@iconcologia.net. FAU - Graas, Marie-Pascale AU - Graas MP AD - Centre Hospitalier Chretien, Liege, Belgium. Electronic address: marie-pascale.graas@chc.be. FAU - Galdermans, Daniella AU - Galdermans D AD - ZNA Middelheim Hospital, Antwerp, Belgium. Electronic address: danny.galdermans@pandora.be. FAU - Vuylsteke, Peter AU - Vuylsteke P AD - Clinique et Maternite Sainte-Elisabeth, Medical Oncology, Namur, Belgium. Electronic address: peter.vuylsteke@cmsenamur.be. FAU - Canon, Jean-Luc AU - Canon JL AD - Grand Hospital de Charleroi, Oncologie-Hematologie, Grand Rue 3, Charleroi 6000, Belgium. Electronic address: jean_luc.canon@ghdc.be. FAU - Schallier, Denis AU - Schallier D AD - Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: denis.schallier@uzbrussel.be. FAU - Decoster, Lore AU - Decoster L AD - Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: lore.decoster@uzbrussel.be. FAU - Teugels, Erik AU - Teugels E AD - Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: Erik.Teugels@uzbrussel.be. FAU - Massey, Dan AU - Massey D AD - Boehringer Ingelheim, Ltd., Bracknell, Berkshire, UK. Electronic address: dan.massey.ext@boehringer-ingelheim.com. FAU - Chand, Vikram K AU - Chand VK AD - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. Electronic address: vikram.chand@boehringer-ingelheim.com. FAU - Vansteenkiste, Johan AU - Vansteenkiste J AD - Respiratory Oncology Unit, Department of Pulmonology, University Hospitals KU Leuven, Leuven, Belgium. Electronic address: johan.vansteenkiste@uz.kuleuven.ac.be. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150123 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antineoplastic Agents) RN - 0 (Quinazolines) RN - 41UD74L59M (Afatinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adenocarcinoma/*drug therapy/mortality MH - Adenocarcinoma of Lung MH - Afatinib MH - Aged MH - Antineoplastic Agents/pharmacokinetics/*therapeutic use MH - DNA Mutational Analysis MH - Disease-Free Survival MH - ErbB Receptors/antagonists & inhibitors/*genetics MH - Female MH - Genotype MH - Humans MH - Lung Neoplasms/*drug therapy/mortality MH - Male MH - Middle Aged MH - Mutation MH - Quinazolines/pharmacokinetics/*therapeutic use MH - Receptor, ErbB-2/antagonists & inhibitors/*genetics MH - Treatment Outcome OTO - NOTNLM OT - Afatinib OT - EGFR OT - ErbB OT - HER2 OT - Non-small cell lung cancer OT - Paclitaxel EDAT- 2015/02/16 06:00 MHDA- 2015/12/15 06:00 CRDT- 2015/02/16 06:00 PHST- 2014/11/28 00:00 [received] PHST- 2015/01/12 00:00 [revised] PHST- 2015/01/16 00:00 [accepted] PHST- 2015/02/16 06:00 [entrez] PHST- 2015/02/16 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S0169-5002(15)00074-4 [pii] AID - 10.1016/j.lungcan.2015.01.013 [doi] PST - ppublish SO - Lung Cancer. 2015 Apr;88(1):63-9. doi: 10.1016/j.lungcan.2015.01.013. Epub 2015 Jan 23.