Patrick Schöffski1, Sant Chawla2, Robert G Maki3, Antoine Italiano4, Hans Gelderblom5, Edwin Choy6, Giovanni Grignani7, Veridiana Camargo8, Sebastian Bauer9, Sun Young Rha10, Jean-Yves Blay11, Peter Hohenberger12, David D'Adamo13, Matthew Guo13, Bartosz Chmielowski14, Axel Le Cesne15, George D Demetri16, Shreyaskumar R Patel17. 1. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: patrick.schoffski@uzleuven.be. 2. Sarcoma Oncology Center, Santa Monica, CA, USA. 3. Tisch Cancer Institute, Mount Sinai Medical Center, New York, NY, USA. 4. Department of Oncology, Institut Bergonié, Bordeaux, France. 5. Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands. 6. Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA. 7. Department of Medical Oncology, Fondazione del Piemonte per I'Oncologia IRCCS, Candiolo, Italy. 8. Department of Medical Oncology, Hospital Sírio-Libanês and Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil. 9. West German Cancer Center, University of Duisburg-Essen, Essen, Germany. 10. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. 11. Université Claude Bernard Lyon I, LYRIC INCa-DGOS 4664 & Centre Léon Bérard, Lyon, France. 12. Division of Surgical Oncology & Thoracic Surgery, Department of Surgery, Mannheim University Medical Center, Mannheim, Germany. 13. Eisai, Woodcliff Lake, NJ, USA. 14. Department of Hematology, UCLA Jonsson Comprehensive Cancer, Los Angeles, CA, USA. 15. Gustave Roussy, Villejuif, France. 16. Sarcoma Center, Dana-Farber Cancer Institute and Ludwig Center at Harvard Medical School, Boston, MA, USA. 17. Department of Sarcoma Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Abstract
BACKGROUND: A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who receiveddacarbazine (an active control). METHODS: We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1·4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue. FINDINGS: Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13·5 months [95% CI 10·9-15·6] vs 11·5 months [9·6-13·0]; hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators. INTERPRETATION:Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma. FUNDING: Eisai.
RCT Entities:
BACKGROUND: A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control). METHODS: We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1·4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue. FINDINGS: Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13·5 months [95% CI 10·9-15·6] vs 11·5 months [9·6-13·0]; hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators. INTERPRETATION: Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma. FUNDING: Eisai.
Authors: Sandra P D'Angelo; Michelle R Mahoney; Brian A Van Tine; James Atkins; Mohammed M Milhem; Balkrishna N Jahagirdar; Cristina R Antonescu; Elise Horvath; William D Tap; Gary K Schwartz; Howard Streicher Journal: Lancet Oncol Date: 2018-01-19 Impact factor: 41.316
Authors: Mrinal M Gounder; Alona Zer; William D Tap; Samer Salah; Mark A Dickson; Abha A Gupta; Mary Louise Keohan; Herbert H Loong; Sandra P D'Angelo; Stephanie Baker; Mercedes Condy; Kjirsten Nyquist-Schultz; Lanier Tanner; Joseph P Erinjeri; Francis H Jasmine; Sharon Friedlander; Robert Carlson; Thaddeus J Unger; Jean-Richard Saint-Martin; Tami Rashal; Joel Ellis; Michael Kauffman; Sharon Shacham; Gary K Schwartz; Albiruni Ryan Abdul Razak Journal: J Clin Oncol Date: 2016-07-25 Impact factor: 44.544