Martin Reck1, Luis Paz-Ares2, Paolo Bidoli3, Federico Cappuzzo4, Shaker Dakhil5, Denis Moro-Sibilot6, Hossein Borghaei7, Melissa Johnson8, Robert Jotte9, Nathan A Pennell10, Frances A Shepherd11, Anne Tsao12, Michael Thomas13, Gebra Cuyun Carter14, Faye Chan-Diehl14, Ekaterine Alexandris14, Pablo Lee14, Annamaria Zimmermann14, Andreas Sashegyi14, Maurice Pérol15. 1. Department of Thoracic Oncology, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Lung Clinic Grosshansdorf, Grosshansdorf, Germany. Electronic address: m.reck@lungenclinic.de. 2. Virgen del Rocio University Hospital, Seville, Spain. 3. Ospedale S Gerardo, Monza, Italy. 4. Istituto Toscano Tumori-Ospedale-Civile-Livorno, Livorno, Italy. 5. Cancer Center of Kansas, Wichita, KS, United States. 6. Thoracic Oncology Unit Teaching Hospital A Michallon, Grenoble, France. 7. Fox Chase Cancer Center, Philadelphia, PA, United States. 8. Sarah Cannon Research Institute, Nashville, TN, United States. 9. Rocky Mountain Cancer Centers, Denver, CO, United States. 10. Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, United States. 11. Princess Margaret Cancer Centre, Toronto, ON, Canada. 12. University of Texas MD Anderson Cancer Center, Houston, TX, United States. 13. Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), German Center for Lung Research (DZL), Heidelberg, Germany. 14. Eli Lilly and Company, Indianapolis, IN, United States. 15. Léon-Bérard Cancer Center, Lyon, France.
Abstract
OBJECTIVES: The REVEL study demonstrated improved efficacy for patients with advanced non-small cell lung cancer treated withramucirumab plus docetaxel, independent of histology. This exploratory analysis characterized the treatment effect in REVEL patients who were refractory to prior first-line treatment. MATERIALS AND METHODS: Refractory patients had a best response of progressive disease to first-line treatment. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and safety. Kaplan-Meier and Cox proportional hazards regression were performed for OS and PFS, and Cochran-Mantel-Haenszel test was used for response. QoL was assessed with the Lung Cancer Symptom Scale. Sensitivity analyses were performed on subgroups of the intent-to-treat population with limited time on first-line therapy. RESULTS:Of 1253 randomized patients in REVEL, 360 (29%) were refractory to first-line treatment. Baseline characteristics were largely balanced between treatment arms. In the control arm, median OS for refractory patients was 6.3 versus 10.3 months for patients not meeting this criterion, demonstrating the poor prognosis of refractory patients. Median OS (8.3 vs. 6.3 months; HR, 0.86; 95% CI, 0.68-1.08), median PFS (4.0 vs. 2.5 months; HR, 0.71; 95% CI, 0.57-0.88), and ORR (22.5% vs. 12.6%) were improved in refractory patients treated with ramucirumab compared to placebo, without new safety concerns or further deteriorating patient QoL. CONCLUSIONS: The effect of ramucirumab in refractory patients is similar to that in the intent-to-treat population. The benefit/risk profile for refractory patients suggests that ramucirumab plus docetaxel is an appropriate treatment option even in this difficult-to-treat population.
RCT Entities:
OBJECTIVES: The REVEL study demonstrated improved efficacy for patients with advanced non-small cell lung cancer treated with ramucirumab plus docetaxel, independent of histology. This exploratory analysis characterized the treatment effect in REVEL patients who were refractory to prior first-line treatment. MATERIALS AND METHODS: Refractory patients had a best response of progressive disease to first-line treatment. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and safety. Kaplan-Meier and Cox proportional hazards regression were performed for OS and PFS, and Cochran-Mantel-Haenszel test was used for response. QoL was assessed with the Lung Cancer Symptom Scale. Sensitivity analyses were performed on subgroups of the intent-to-treat population with limited time on first-line therapy. RESULTS: Of 1253 randomized patients in REVEL, 360 (29%) were refractory to first-line treatment. Baseline characteristics were largely balanced between treatment arms. In the control arm, median OS for refractory patients was 6.3 versus 10.3 months for patients not meeting this criterion, demonstrating the poor prognosis of refractory patients. Median OS (8.3 vs. 6.3 months; HR, 0.86; 95% CI, 0.68-1.08), median PFS (4.0 vs. 2.5 months; HR, 0.71; 95% CI, 0.57-0.88), and ORR (22.5% vs. 12.6%) were improved in refractory patients treated with ramucirumab compared to placebo, without new safety concerns or further deteriorating patient QoL. CONCLUSIONS: The effect of ramucirumab in refractory patients is similar to that in the intent-to-treat population. The benefit/risk profile for refractory patients suggests that ramucirumab plus docetaxel is an appropriate treatment option even in this difficult-to-treat population.
Authors: Alain Vergnenègre; Victor Basse; Gwenaelle Le Garff; Olivier Bylicki; Catherine Dubos-Arvis; Bénédicte Comet; Marie Marcq; Jacques Le Treut; Jean-Bernard Auliac; Anne Madroszyk; Gislaine Fraboulet; Jacky Crequit; Pascal Thomas; Nicolas Paleiron; Isabelle Monnet Journal: Cancer Manag Res Date: 2019-12-27 Impact factor: 3.989
Authors: Edward B Garon; Katherine B Winfree; Cliff Molife; Zhanglin Lin Cui; Edurne Arriola; Benjamin Levy; Tarek Mekhail; Maurice Pérol Journal: Support Care Cancer Date: 2020-04-21 Impact factor: 3.603
Authors: Edward B Garon; Giorgio Vittorio Scagliotti; Oliver Gautschi; Martin Reck; Michael Thomas; Lara Iglesias Docampo; Haralabos Kalofonos; Joo-Hang Kim; Steven Gans; Odd Terje Brustugun; Sergey V Orlov; Gebra Cuyun Carter; Annamaria H Zimmermann; Ana B Oton; Ekaterine Alexandris; Pablo Lee; Katharina Wolff; Victoria Jennifer Stefaniak; Mark A Socinski; Maurice Pérol Journal: ESMO Open Date: 2020-01
Authors: Jeronimo Rafael Rodríguez-Cid; Saul Campos-Gomez; Vanessa García-Montes; Manuel Magallanes-Maciel; Rodrigo Rafael Flores-Mariñelarena; Valeria Michelle Fernández-Garibay; Iván Romarico González-Espinoza; Juan Paulo Ceja-García; Juan Carlos Cázarez-Price; Luis Martínez-Barrera; Leopoldo Barriguete-Parra; Carlos Jose Zuloaga-Fernandez; Roberto Kuri-Exsome; David Suárez-García; Jorge Ignacio Gonzalez-Villanueva; Noé Flores-Anaya; Jose Antonio Acevedo-Delgado; Alma Magdalena Astorga-Ramos; Raquel Gerson-Cwilich; Alberto Villalobos-Prieto; Claudia Rodríguez-Silva; Maria Fernanda Noriega-Iriondo; Leticia Vázquez-Cortés; Eusebio Perales-Rodríguez; Alicia Acosta-Espinoza; Yareni Perez-Lozano; Daniel Capdeville-García; Jorge Arturo Alatorre-Alexander Journal: JCO Glob Oncol Date: 2020-03