Martin Reck1, Anders Mellemgaard2, Joachim von Pawel3, Maya Gottfried4, Igor Bondarenko5, Ying Cheng6, Kostas Zarogoulidis7, Alexander Luft8, Jaafar Bennouna9, José Barrueco10, Hesham Aboshady10, Julia Hocke11, Rolf Kaiser11, Jean-Yves Douillard9. 1. 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. 2. Department of Oncology, Herlev University Hospital, Herlev, Denmark. 3. Pneumology Clinic, Asklepios Fachkliniken, Gauting, Germany. 4. Lung Cancer Unit, Meir Medical Center, Kfar Saba, Israel. 5. Clinical Facility, Dnepropetrovsk Medical Academy, Clinical Hospital #4, Dnepropetrovsk, Ukraine. 6. Division of Thoracic Oncology, Jilin Province Cancer Hospital, Changchun, China. 7. Pulmonary Department-Oncology Unit, General Hospital of Thessaloniki, Thessaloniki, Greece. 8. Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, St. Petersburg, Russia. 9. Department of Medical Oncology, Centre René Gauducheau, Nantes, France. 10. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. 11. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Abstract
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.
RCT Entities:
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.
Authors: Maya Gottfried; Jaafar Bennouna; Igor Bondarenko; Jean-Yves Douillard; David F Heigener; Maciej Krzakowski; Anders Mellemgaard; Silvia Novello; Sergei Orlov; Yvonne Summers; Joachim von Pawel; Julia Stöhr; Rolf Kaiser; Martin Reck Journal: Target Oncol Date: 2017-08 Impact factor: 4.493
Authors: Ana L M Batista de Carvalho; Paula S C Medeiros; Francisco M Costa; Vanessa P Ribeiro; Joana B Sousa; Carmen Diniz; Maria P M Marques Journal: PLoS One Date: 2016-11-23 Impact factor: 3.240