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.

Lorenzo D'Ambrosio, Nathan Touati, Jean-Yves Blay, Giovanni Grignani, Ronan Flippot, Anna M. Czarnecka, Sophie Piperno-Neumann, Javier Martin-Broto, Roberta Sanfilippo, Daniela Katz, Florence Duffaud, Bruno Vincenzi, Daniel P. Stark, Filomena Mazzeo, Armin Tuchscherer, Christine Chevreau, Jenny Sherriff, Anna Estival, Saskia Litière, Ward SentsIsabelle Ray-Coquard, Francesco Tolomeo, Axel Le Cesne, Piotr Rutkowski, Silvia Stacchiotti, Bernd Kasper, Hans Gelderblom, Alessandro Gronchi

Research output: Contribution to journalArticlepeer-review

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 (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.
Original languageEnglish
JournalCancer
Issue number11
Publication statusPublished - Jun 1 2020

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