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,Daniel P Stark,Jenny Sherriff,Axel Le Cesne,Ward Sents,Bernd Kasper,Isabelle Ray‐Coquard,Anna M Czarnecka,Florence Duffaud,Armin Tuchscherer,Ronan Flippot,Christine Chevreau,Silvia Stacchiotti,Giovanni Grignani,Anna Estival,Saskia Litière,Alessandro Gronchi,Bruno Vincenzi,Daniela Katz,Sophie Piperno‐Neumann,Roberta Sanfilippo,Francesco Tolomeo,Jean‐Yves Blay,Nathan Touati,Hans Gelderblom,Javier Martín-Broto ,F Mazzeo

doi:10.1002/cncr.32795

Abstract

The optimal treatment for advanced leiomyosarcoma is still debated. Givenhistotype-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. 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≥18years. 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. 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 9.2months (95% confidence interval [CI], 5.2-9.7months), 8.2months (95% CI, 5.2-10.1months), and 4.8months (95% CI, 2.3-6.0months) 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, 36.8months; 95% CI, 27.9-47.2months) in comparison with both doxorubicin plus ifosfamide (median, 21.9months; 95% CI, 16.7-33.4months; HR, 0.65; 95% CI, 0.40-1.06) and doxorubicin (median, 30.3months; 95% CI, 21.0-36.3months; 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. 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.

Highlights

Soft tissue sarcomas (STS) are a heterogeneous group of tumors encompassing more than 50 different entities
These results favorably compare with both historical controls and the results observed with either doxorubicin+ifosfamide or doxorubicin alone in our study.[13,36,37,38]
Retrospective, the outcomes observed in the doxorubicin alone and in the doxorubicin+ifosfamide arms are consistent with the ones reported in the randomized EORTC 62012 study using the same regimens [median progression-free survival (PFS) for leiomyosarcoma patients: 6.1 and 6.6 months, respectively]

Summary

Introduction

Soft tissue sarcomas (STS) are a heterogeneous group of tumors encompassing more than 50 different entities. In the lack of histotype-specific prospective controlled data, we retrospectively evaluated doxorubicin+dacarbazine, doxorubicin+ifosfamide and doxorubicin alone as first-line treatment for advanced/metastatic leiomyosarcoma treated within EORTC-STBSG sites. Patients were matched according to their propensity scores estimated using a logistic regression model accounting for histology, grade, age, gender, performance status, tumor site and extent. In the 2:1:2 propensity score-matched population (205 patients), estimated median PFS was 9.2 (5.2-97), 8.2 (5.2-10.1), and 4.8 months (2.3-6.0), with an ORR of 30.9%, 19.5%, and 25.6% for doxorubicin+dacarbazine, doxorubicin+ifosfamide, and doxorubicin alone, respectively. In the propensity score-matched population doxorubicin+dacarbazine showed favorable activity in terms of both ORR and PFS warranting further evaluation in prospective trials

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Conclusion