Lorenzo D'Ambrosio1,2, Nathan Touati3, Jean-Yves Blay4, Giovanni Grignani2, Ronan Flippot5, Anna M Czarnecka6,7, Sophie Piperno-Neumann8, Javier Martin-Broto9, Roberta Sanfilippo10, Daniela Katz11, Florence Duffaud12, Bruno Vincenzi13, Daniel P Stark14, Filomena Mazzeo15, Armin Tuchscherer16, Christine Chevreau17, Jenny Sherriff18, Anna Estival19, Saskia Litière3, Ward Sents3, Isabelle Ray-Coquard4, Francesco Tolomeo2, Axel Le Cesne5, Piotr Rutkowski6,7, Silvia Stacchiotti10, Bernd Kasper20, Hans Gelderblom21, Alessandro Gronchi22. 1. Department of Oncology, University of Turin, Turin, Italy. 2. Sarcoma Unit, Division of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy. 3. European Organization for Research and Treatment of Cancer, Brussels, Belgium. 4. Leon Berard Center and Claude Bernard Lyon I University, EURACAN, LYRICAN, Lyon, France. 5. Department of Medicine, Gustave Roussy, Villejuif Cedex, France. 6. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute-Oncology Center, Gliwice, Poland. 7. Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. 8. Medical Oncology Department, Curie Institute, Paris, France. 9. Virgen del Rocio University Hospital, Institute of Biomedicine Research/CSIC/University of Seville, Seville, Spain. 10. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 11. Oncology Department, Sharett Institute of Oncology, Hadassah-Hebrew University, Jerusalem, Israel. 12. Medical Oncology - University Hospital Timone, Aix-Marseille University, Marseille, France. 13. Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy. 14. St James's Institute of Oncology, Leeds Institute of Cancer and Pathology, University of Leeds and Leeds Teaching Hospitals National Health Service Trust, Leeds, United Kingdom. 15. Medical Oncology, Clinique Universitaire Saint-Luc, Woluwe-Saint-Lambert, Belgium. 16. Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany. 17. Claudius Regaud Institute, University Cancer Institute of Toulouse, Toulouse, France. 18. Cancer Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom. 19. Catalan Institute of Oncology, Barcelona, Spain. 20. Sarcoma Unit, Interdisciplinary Tumor Center, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany. 21. Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands. 22. Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
BACKGROUND: The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype-specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first-line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) sites. METHODS: The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval-censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent. RESULTS: Three hundred three patients from 18 EORTC-STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score-matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2-9.7 months), 8.2 months (95% CI, 5.2-10.1 months), and 4.8 months (95% CI, 2.3-6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7-33.4 months; HR, 0.65; 95% CI, 0.40-1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0-36.3 months; HR, 0.66; 95% CI, 0.43-0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS. CONCLUSIONS: This is the largest retrospective study of first-line treatment for advanced leiomyosarcoma. In the propensity score-matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials.
BACKGROUND: The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype-specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first-line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) sites. METHODS: The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval-censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent. RESULTS: Three hundred three patients from 18 EORTC-STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score-matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2-9.7 months), 8.2 months (95% CI, 5.2-10.1 months), and 4.8 months (95% CI, 2.3-6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7-33.4 months; HR, 0.65; 95% CI, 0.40-1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0-36.3 months; HR, 0.66; 95% CI, 0.43-0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS. CONCLUSIONS: This is the largest retrospective study of first-line treatment for advanced leiomyosarcoma. In the propensity score-matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials.
Authors: Ignacio Campillo-Marcos; Eva Monte-Serrano; Elena Navarro-Carrasco; Raúl García-González; Pedro A Lazo Journal: Front Cell Dev Biol Date: 2021-09-03
Authors: Bernd Kasper; Lorenzo D'Ambrosio; Elizabeth J Davis; Matthew Ingham; Javier Martin Broto; Jonathan C Trent; Winan J van Houdt; Brian A Van Tine Journal: Curr Treat Options Oncol Date: 2022-03-11