TY - JOUR
T1 - Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
AU - D'Ambrosio, Lorenzo
AU - Touati, Nathan
AU - Blay, Jean-Yves
AU - Grignani, Giovanni
AU - Flippot, Ronan
AU - Czarnecka, Anna M.
AU - Piperno-Neumann, Sophie
AU - Martin-Broto, Javier
AU - Sanfilippo, Roberta
AU - Katz, Daniela
AU - Duffaud, Florence
AU - Vincenzi, Bruno
AU - Stark, Daniel P.
AU - Mazzeo, Filomena
AU - Tuchscherer, Armin
AU - Chevreau, Christine
AU - Sherriff, Jenny
AU - Estival, Anna
AU - Litière, Saskia
AU - Sents, Ward
AU - Ray-Coquard, Isabelle
AU - Tolomeo, Francesco
AU - Le Cesne, Axel
AU - Rutkowski, Piotr
AU - Stacchiotti, Silvia
AU - Kasper, Bernd
AU - Gelderblom, Hans
AU - Gronchi, Alessandro
N1 - Place: United States
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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 (95CI], 5.2-9.7 months), 8.2 months (95 5.2-10.1 months), and 4.8 months (95 2.3-6.0 months) with ORRs of 30.9 19.5 and 25.6 doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95 16.7-33.4 months; HR, 0.65; 95 0.40-1.06) and doxorubicin (median, 30.3 months; 95 21.0-36.3 months; HR, 0.66; 95 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.
AB - 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 (95CI], 5.2-9.7 months), 8.2 months (95 5.2-10.1 months), and 4.8 months (95 2.3-6.0 months) with ORRs of 30.9 19.5 and 25.6 doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95 16.7-33.4 months; HR, 0.65; 95 0.40-1.06) and doxorubicin (median, 30.3 months; 95 21.0-36.3 months; HR, 0.66; 95 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.
M3 - Article
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 11
ER -