A Le Cesne1, J-Y Blay2, D Cupissol3, A Italiano4, C Delcambre5, N Penel6, N Isambert7, C Chevreau8, E Bompas9, F Bertucci10, L Chaigneau11, S Piperno-Neumann12, S Salas13, M Rios14, C Guillemet15, J-O Bay16, I Ray-Coquard2, L Haddag17, J Bonastre18, R Kapso18, A Fraslin18, N Bouvet19, O Mir20, S Foulon18. 1. Medical Oncology Department, Gustave Roussy, Villejuif, France. Electronic address: axel.lecesne@gustaveroussy.fr. 2. Medical Oncology Department, Centre Léon Bérard and Claude Bernard University, Lyon, France. 3. Medical Oncology Department, Centre Val d'Aurelle, Montpellier, France. 4. Medical Oncology Department, Institut Bergonié, Bordeaux, France. 5. Medical Oncology Department, Centre François Baclesse, Caen, France. 6. Medical Oncology Department, Centre Oscar Lambret and Lille University, Lille, France. 7. Medical Oncology Department, Centre Georges-François Leclerc, Dijon, France. 8. Medical Oncology Department, Institut Claudius Regaud, Toulouse, France. 9. Medical Oncology Department, Centre René Gauduchau, Nantes, France. 10. Medical Oncology Department, Institut Paoli-Calmettes, Marseille, France. 11. Medical Oncology Department, Hôpital Jean Minjoz, Besancon, France. 12. Medical Oncology Department, Insitut Curie, Paris, France. 13. Medical Oncology Department, Hôpital La Timone, Marseille, France. 14. Medical Oncology Department, Institut de Cancerologie de Lorraine, Nancy, France. 15. Medical Oncology Department, Centre Henri Becquerel, Rouen, France. 16. Medical Oncology Department, Centre Jean Perrin, Clermont Ferrand, France. 17. Department of Radiology, Gustave Roussy, Villejuif, France. 18. Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France; Oncostat U1018, Inserm, University Paris-Saclay, Labeled Ligue Contre le Cancer, Villejuif, France. 19. Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France. 20. Medical Oncology Department, Gustave Roussy, Villejuif, France.
Abstract
BACKGROUND: The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m2 every 3 weeks or BSC, stratified into L-STS (liposarcoma/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from the BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. RESULTS:Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of CancerQuality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. CONCLUSION:Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.
RCT Entities:
BACKGROUND: The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m2 every 3 weeks or BSC, stratified into L-STS (liposarcoma/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from the BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. RESULTS: Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. CONCLUSION: Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.
Authors: Michael J Wagner; Yuzheng Zhang; Lee D Cranmer; Elizabeth T Loggers; Graeme Black; Sabrina McDonnell; Shannon Maxwell; Rylee Johnson; Roxanne Moore; Pedro Hermida de Viveiros; Lauri Aicher; Kimberly S Smythe; Qianchuan He; Robin L Jones; Seth M Pollack Journal: Clin Cancer Res Date: 2022-06-01 Impact factor: 13.801