Patrick Schöffski1, Maud Toulmonde2, Anna Estival3, Gloria Marquina4, Monika Dudzisz-Śledź5, Mehdi Brahmi6, Neeltje Steeghs7, Vasilios Karavasilis8, Jacco de Haan9, Agnieszka Wozniak10, Sophie Cousin2, Marta Domènech3, Judith V M G Bovée11, Céline Charon-Barra12, Sandrine Marreaud13, Saskia Litière13, Laura De Meulemeester13, Christine Olungu13, Hans Gelderblom14. 1. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of Oncology, KU Leuven, Laboratory of Experimental Oncology, Leuven, Belgium. Electronic address: patrick.schoffski@uzleuven.be. 2. Sarcoma Unit, Institut Bergonié, Bordeaux, France. 3. Department of Medical Oncology, Catalan Institute of Oncology (ICO) Badalona / Hospital Germans Trias I Pujol. B-ARGO, Barcelona, Spain. 4. Department of General Medical Oncology, Hospital Clinico San Carlos, Madrid, Spain. 5. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 6. Centre Léon Bérard, Université Cl. Bernard Lyon 1, Lyon, France. 7. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. 8. University College Hospital, London, United Kingdom. 9. University Medical Center, Groningen, the Netherlands. 10. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of Oncology, KU Leuven, Laboratory of Experimental Oncology, Leuven, Belgium. 11. Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. 12. Department of Pathology, Centre Georges-François Leclerc, Dijon, France. 13. European Organization for Research and Treatment of Cancer, Brussels, Belgium. 14. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Abstract
PURPOSE:EORTC-1506-STBSG was a prospective, multicentric, randomised, open-label phase 2 trial to assess the efficacy and safety of second-line nintedanib versus ifosfamide in patients with advanced, inoperable metastatic soft tissue sarcoma (STS). The primary end-point was progression-free survival. PATIENTS/ METHODS:Patients with a variety of STS subtypes were randomised 1:1 to nintedanib (200 mg b.i.d. p.o. until disease progression) or ifosfamide (3 g/m2 i.v. days 1-3, every 21 days for ≤6 cycles). A Korn design was applied aiming to detect an improvement in median progression-free survival (mPFS) from 3 to 4.5 months (HR = 0.667). An interim look was incorporated to stop the trial for futility if <19 of the first 36 patients treated with nintedanib were progression-free at week 12. RESULTS: At the interim analysis, among the first 36 eligible and evaluable patients randomised for nintedanib, only 13 (36%) were progression-free at week 12. The trial was closed for further accrual as per protocol. In total, 80 patients were randomised (40 per treatment group). The mPFS was 2.5 months (95% CI: 1.5-3.4) for nintedanib and 4.4 months (95% CI: 2.9-6.7) on ifosfamide (adjusted HR = 1.56 [80% CI: 1.14-2.13], p = 0.070). The median overall survival was 13.7 months (95% CI: 9.4-23.4) on nintedanib and 24.1 months (95% CI: 10.9-NE) on ifosfamide (adjusted HR = 1.65 [95%CI:0.89-3.06], p = 0.111). The clinical benefit rate for nintedanib and ifosfamide was 50% versus 62.5% (p = 0.368), respectively. Common treatment-related adverse events (all grades) were diarrhoea (35.9% of patients), fatigue (25.6%) and nausea (20.5%) for nintedanib; and fatigue (52.6%), nausea (44.7%) and vomiting, anorexia and alopecia (28.9% each) for ifosfamide. CONCLUSION: The trial was stopped for futility. The activity of nintedanib did not warrant further exploration in non-selected, advanced STSs.
RCT Entities:
PURPOSE:EORTC-1506-STBSG was a prospective, multicentric, randomised, open-label phase 2 trial to assess the efficacy and safety of second-line nintedanib versus ifosfamide in patients with advanced, inoperable metastatic soft tissue sarcoma (STS). The primary end-point was progression-free survival. PATIENTS/ METHODS:Patients with a variety of STS subtypes were randomised 1:1 to nintedanib (200 mg b.i.d. p.o. until disease progression) or ifosfamide (3 g/m2 i.v. days 1-3, every 21 days for ≤6 cycles). A Korn design was applied aiming to detect an improvement in median progression-free survival (mPFS) from 3 to 4.5 months (HR = 0.667). An interim look was incorporated to stop the trial for futility if <19 of the first 36 patients treated with nintedanib were progression-free at week 12. RESULTS: At the interim analysis, among the first 36 eligible and evaluable patients randomised for nintedanib, only 13 (36%) were progression-free at week 12. The trial was closed for further accrual as per protocol. In total, 80 patients were randomised (40 per treatment group). The mPFS was 2.5 months (95% CI: 1.5-3.4) for nintedanib and 4.4 months (95% CI: 2.9-6.7) on ifosfamide (adjusted HR = 1.56 [80% CI: 1.14-2.13], p = 0.070). The median overall survival was 13.7 months (95% CI: 9.4-23.4) on nintedanib and 24.1 months (95% CI: 10.9-NE) on ifosfamide (adjusted HR = 1.65 [95%CI:0.89-3.06], p = 0.111). The clinical benefit rate for nintedanib and ifosfamide was 50% versus 62.5% (p = 0.368), respectively. Common treatment-related adverse events (all grades) were diarrhoea (35.9% of patients), fatigue (25.6%) and nausea (20.5%) for nintedanib; and fatigue (52.6%), nausea (44.7%) and vomiting, anorexia and alopecia (28.9% each) for ifosfamide. CONCLUSION: The trial was stopped for futility. The activity of nintedanib did not warrant further exploration in non-selected, advanced STSs.