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

D'Ambrosio, L.; Touati, N.; Blay, J.Y.; Grignani, G.; Flippot, R.; Czarnecka, A.M.; ... ; Treatment Canc Soft Tissue Bone Sa (2020)

Article / Letter to editor

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.

• dacarbazine
• doxorubicin
• ifosfamide
• leiomyosarcoma
• sarcoma
• propensity score
• retrospective study

• All authors: D'Ambrosio, L.; Touati, N.; Blay, J.Y.; Grignani, G.; Flippot, R.; Czarnecka, A.M.; Piperno-Neumann, S.; Martin-Broto, J.; Sanfilippo, R.; Katz, D.; Duffaud, F.; Vincenzi, B.; Stark, D.P.; Mazzeo, F.; Tuchscherer, A.; Chevreau, C.; Sherriff, J.; Estival, A.; Litiere, S.; Sents, W.; Ray-Coquard, I.; Tolomeo, F.; Cesne, A. le; Rutkowski, P.; Stacchiotti, S.; Kasper, B.; Gelderblom, H.; Gronchi, A.; European Org Res; Treatment Canc Soft Tissue Bone Sa
• Date: 2020-06-01
• Journal: Cancer
• Volume: 126
• Issue: 11
• Pages: 2637 - 2647
• DOI: doi:10.1002/cncr.32795
• Link: https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32795