PMID- 26415992 OWN - NLM STAT- MEDLINE DCOM- 20160803 LR - 20181202 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 90 IP - 2 DP - 2015 Nov TI - Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel. PG - 267-73 LID - S0169-5002(15)30027-1 [pii] LID - 10.1016/j.lungcan.2015.08.003 [doi] AB - OBJECTIVES: LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial investigating nintedanib+docetaxel versus placebo+docetaxel in patients with advanced NSCLC progressing after first-line chemotherapy. Progression-free survival was significantly improved with nintedanib+docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents. MATERIALS AND METHODS: The incidence and intensity of AEs were evaluated in all patients who received at least one dose of study medication (N=1307) and for the two main histologies: adenocarcinoma (n=653) and squamous cell carcinoma (SCC; n=553). AEs of special interest were analyzed by category, preferred term, and worst CTCAE grade and included perforation, hypertension, bleeding, thromboembolic events, and skin disorders. RESULTS AND CONCLUSION: The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib+docetaxel versus 0.2% with placebo+docetaxel. The incidence of some events was higher with nintedanib+docetaxel versus placebo+docetaxel; hypertension (3.5% vs 0.9%), rash (11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and cutaneous adverse reactions were predominantly Grade 1-2 with both treatments. The incidence of all-grade bleeding was also slightly higher in nintedanib+docetaxel-treated patients (14.1% vs 11.6%) driven by between-treatment differences in the SCC subpopulation; most events were Grade 1-2. The proportion of patients with a thromboembolic event was low and comparable between arms for all grades (5.1% vs 4.6%) and Grade >/=3 (2.1% vs 3.1%). Safety evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly associated with other anti-angiogenic agents was lower with nintedanib+docetaxel. Survival benefits from addition of nintedanib to docetaxel in patients with adenocarcinoma after first-line therapy can be achieved alongside a manageable safety profile. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Reck, Martin AU - Reck M AD - Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany. Electronic address: Dr.martin.reck@web.de. FAU - Mellemgaard, Anders AU - Mellemgaard A AD - Department of Oncology, Herlev University Hospital, Herlev, Denmark. FAU - von Pawel, Joachim AU - von Pawel J AD - Pneumology Clinic, Asklepios Fachkliniken, Gauting, Germany. FAU - Gottfried, Maya AU - Gottfried M AD - Lung Cancer Unit, Meir Medical Center, Kfar Saba, Israel. FAU - Bondarenko, Igor AU - Bondarenko I AD - Clinical Facility, Dnepropetrovsk Medical Academy, Clinical Hospital #4, Dnepropetrovsk, Ukraine. FAU - Cheng, Ying AU - Cheng Y AD - Division of Thoracic Oncology, Jilin Province Cancer Hospital, Changchun, China. FAU - Zarogoulidis, Kostas AU - Zarogoulidis K AD - Pulmonary Department-Oncology Unit, General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Luft, Alexander AU - Luft A AD - Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, St. Petersburg, Russia. FAU - Bennouna, Jaafar AU - Bennouna J AD - Department of Medical Oncology, Centre Rene Gauducheau, Nantes, France. FAU - Barrueco, Jose AU - Barrueco J AD - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. FAU - Aboshady, Hesham AU - Aboshady H AD - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. FAU - Hocke, Julia AU - Hocke J AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Kaiser, Rolf AU - Kaiser R AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Douillard, Jean-Yves AU - Douillard JY AD - Department of Medical Oncology, Centre Rene Gauducheau, Nantes, France. CN - LUME-Lung 1 Study Group LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150812 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Indoles) RN - 0 (Taxoids) RN - 15H5577CQD (Docetaxel) RN - G6HRD2P839 (nintedanib) SB - IM MH - Adenocarcinoma/drug therapy MH - Angiogenesis Inhibitors/*adverse effects/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Carcinoma, Squamous Cell/drug therapy MH - Disease-Free Survival MH - Docetaxel MH - Humans MH - Indoles/administration & dosage/adverse effects MH - Lung Neoplasms/*drug therapy MH - Taxoids/administration & dosage/adverse effects MH - Treatment Outcome OTO - NOTNLM OT - Angiogenesis inhibitors OT - Drug-related side effects and adverse reactions OT - Non-small cell lung cancer EDAT- 2015/09/30 06:00 MHDA- 2016/08/04 06:00 CRDT- 2015/09/30 06:00 PHST- 2015/06/11 00:00 [received] PHST- 2015/08/04 00:00 [revised] PHST- 2015/08/08 00:00 [accepted] PHST- 2015/09/30 06:00 [entrez] PHST- 2015/09/30 06:00 [pubmed] PHST- 2016/08/04 06:00 [medline] AID - S0169-5002(15)30027-1 [pii] AID - 10.1016/j.lungcan.2015.08.003 [doi] PST - ppublish SO - Lung Cancer. 2015 Nov;90(2):267-73. doi: 10.1016/j.lungcan.2015.08.003. Epub 2015 Aug 12.