Maya Gottfried1, Jaafar Bennouna2, Igor Bondarenko3, Jean-Yves Douillard2, David F Heigener4, Maciej Krzakowski5, Anders Mellemgaard6, Silvia Novello7, Sergei Orlov8, Yvonne Summers9, Joachim von Pawel10, Julia Stöhr11, Rolf Kaiser12,13, Martin Reck4. 1. Lung Cancer Unit, Meir Medical Center, 4428164, Kfar Saba, Israel. Maya.Gottfried@clalit.org.il. 2. Département D'Oncologie Médicale, ICO René Gauducheau, 44805, Saint Herblain Cedex, France. 3. Dnepropetovsk Medical Academy, Municipal Clinical Hospital #4, Dnipropetrovsk, 49102, Ukraine. 4. Department of Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 22927, Grosshansdorf, Germany. 5. Oncology Institute, 02-781, Warsaw, Poland. 6. Department of Oncology, Herlev Hospital, 2730, Herlev, Denmark. 7. Thoracic Oncology Unit, AUO San Luigi, Department of Oncology, University of Turin, 10124, Torino, Italy. 8. Department of Thoracic Oncology, GOU VPO St Petersburg State Medical University, St Petersburg, 197022, Russia. 9. Department of Medical Oncology, Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UK. 10. Asklepios Fachkliniken München-Gauting, 82131, Gauting, Germany. 11. Boehringer Ingelheim Pharma GmbH & Co. KG, 88400, Biberach, Germany. 12. Boehringer Ingelheim Pharma GmbH & Co. KG, 55216, Ingelheim am Rhein, Germany. 13. Johannes Gutenberg University of Mainz, 55122, Mainz, Germany.
Abstract
BACKGROUND: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months. OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT. PATIENTS AND METHODS: Exploratory analyses were conducted of the overall and European LUME-Lung 1 adenocarcinoma population according to age, prior therapy, and tumor dynamics. Analyses also used TSFLT and time from end of FLT (TEFLT). RESULTS: Treatment with nintedanib/docetaxel significantly improved OS in European patients independently of age or prior therapy. Analyses of several patient subgroups showed improvements in median OS: TSFLT <6 months, 9.5 versus 7.5 months (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.55-0.98); chemorefractory to FLT, 9.1 versus 6.9 months (HR 0.72, 95% CI 0.52-0.99); progressive disease (PD) as best response to FLT, 9.8 versus 6.3 months (HR 0.62, 95% CI 0.41-0.94); TEFLT ≤6 months, 11.3 versus 8.2 months (HR 0.75, 95% CI 0.61-0.92); and TEFLT <3 months, 11.0 versus 8.0 months (HR 0.74, 95% CI 0.58-0.94). CONCLUSIONS:Nintedanib/docetaxel demonstrated significant OS benefits in adenocarcinoma patients, which were more pronounced in patients with shorter TSFLT or TEFLT, or with PD as best response to FLT. This study was registered at ClinicalTrials.gov: NCT00805194.
RCT Entities:
BACKGROUND:Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinomapatients and those with time from start of FLT (TSFLT) <9 months. OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinomapatients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT. PATIENTS AND METHODS: Exploratory analyses were conducted of the overall and European LUME-Lung 1 adenocarcinoma population according to age, prior therapy, and tumor dynamics. Analyses also used TSFLT and time from end of FLT (TEFLT). RESULTS: Treatment with nintedanib/docetaxel significantly improved OS in European patients independently of age or prior therapy. Analyses of several patient subgroups showed improvements in median OS: TSFLT <6 months, 9.5 versus 7.5 months (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.55-0.98); chemorefractory to FLT, 9.1 versus 6.9 months (HR 0.72, 95% CI 0.52-0.99); progressive disease (PD) as best response to FLT, 9.8 versus 6.3 months (HR 0.62, 95% CI 0.41-0.94); TEFLT ≤6 months, 11.3 versus 8.2 months (HR 0.75, 95% CI 0.61-0.92); and TEFLT <3 months, 11.0 versus 8.0 months (HR 0.74, 95% CI 0.58-0.94). CONCLUSIONS:Nintedanib/docetaxel demonstrated significant OS benefits in adenocarcinomapatients, which were more pronounced in patients with shorter TSFLT or TEFLT, or with PD as best response to FLT. This study was registered at ClinicalTrials.gov: NCT00805194.
Authors: Denis Moro-Sibilot; Egbert Smit; Javier de Castro Carpeño; Krzysztof Lesniewski-Kmak; Joachim Aerts; Rosa Villatoro; Kees Kraaij; Karim Nacerddine; Yulia Dyachkova; Karen T Smith; Kaisa Taipale; Allicia C Girvan; Carla Visseren-Grul; Philipp A Schnabel Journal: Lung Cancer Date: 2015-02-21 Impact factor: 5.705
Authors: J von Pawel; J H Schiller; F A Shepherd; S Z Fields; J P Kleisbauer; N G Chrysson; D J Stewart; P I Clark; M C Palmer; A Depierre; J Carmichael; J B Krebs; G Ross; S R Lane; R Gralla Journal: J Clin Oncol Date: 1999-02 Impact factor: 44.544
Authors: Nasser Hanna; Frances A Shepherd; Frank V Fossella; Jose R Pereira; Filippo De Marinis; Joachim von Pawel; Ulrich Gatzemeier; Thomas Chang Yao Tsao; Miklos Pless; Thomas Muller; Hong-Liang Lim; Christopher Desch; Klara Szondy; Radj Gervais; Christian Manegold; Sofia Paul; Paolo Paoletti; Lawrence Einhorn; Paul A Bunn Journal: J Clin Oncol Date: 2004-05-01 Impact factor: 44.544
Authors: Giorgio Scagliotti; Nasser Hanna; Frank Fossella; Katherine Sugarman; Johannes Blatter; Patrick Peterson; Lorinda Simms; Frances A Shepherd Journal: Oncologist Date: 2009-02-16
Authors: Hossein Borghaei; Luis Paz-Ares; Leora Horn; David R Spigel; Martin Steins; Neal E Ready; Laura Q Chow; Everett E Vokes; Enriqueta Felip; Esther Holgado; Fabrice Barlesi; Martin Kohlhäufl; Oscar Arrieta; Marco Angelo Burgio; Jérôme Fayette; Hervé Lena; Elena Poddubskaya; David E Gerber; Scott N Gettinger; Charles M Rudin; Naiyer Rizvi; Lucio Crinò; George R Blumenschein; Scott J Antonia; Cécile Dorange; Christopher T Harbison; Friedrich Graf Finckenstein; Julie R Brahmer Journal: N Engl J Med Date: 2015-09-27 Impact factor: 91.245
Authors: Martin Reck; Anders Mellemgaard; Joachim von Pawel; Maya Gottfried; Igor Bondarenko; Ying Cheng; Kostas Zarogoulidis; Alexander Luft; Jaafar Bennouna; José Barrueco; Hesham Aboshady; Julia Hocke; Rolf Kaiser; Jean-Yves Douillard Journal: Lung Cancer Date: 2015-08-12 Impact factor: 5.705
Authors: Giorgio Vittorio Scagliotti; Purvish Parikh; Joachim von Pawel; Bonne Biesma; Johan Vansteenkiste; Christian Manegold; Piotr Serwatowski; Ulrich Gatzemeier; Raghunadharao Digumarti; Mauro Zukin; Jin S Lee; Anders Mellemgaard; Keunchil Park; Shehkar Patil; Janusz Rolski; Tuncay Goksel; Filippo de Marinis; Lorinda Simms; Katherine P Sugarman; David Gandara Journal: J Clin Oncol Date: 2008-05-27 Impact factor: 44.544
Authors: Edward S Kim; Vera Hirsh; Tony Mok; Mark A Socinski; Radj Gervais; Yi-Long Wu; Long-Yun Li; Claire L Watkins; Mark V Sellers; Elizabeth S Lowe; Yan Sun; Mei-Lin Liao; Kell Osterlind; Martin Reck; Alison A Armour; Frances A Shepherd; Scott M Lippman; Jean-Yves Douillard Journal: Lancet Date: 2008-11-22 Impact factor: 79.321
Authors: D Isla; J de Castro; R García-Campelo; P Lianes; E Felip; P Garrido; L Paz-Ares; J M Trigo Journal: Clin Transl Oncol Date: 2019-07-31 Impact factor: 3.405