A phase II of gemcitabine combined with pazopanib followed by pazopanib maintenance, as second-line treatment in patients with advanced leiomyosarcomas: A unicancer French Sarcoma Group study (LMS03 study).

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Auteur: 
Pautier, P; Penel, N; Ray-Coquard, I; Chenuc, G; Duffaud, F
Date Publication: 
2020
Mois: 
Janvier
Revue: 
European journal of cancer (Oxford, England : 1990)
ISSN: 
1879-0852
NLM-ID: 
9005373
Volume: 
125
Page: 
31-37
Résumé: 
Options in second-line therapy after doxorubicin-based chemotherapy for metastatic/advanced leiomyosarcoma include gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently, no combination therapy is better than monotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and tolerance of G + P in the second-line setting.Patients (pts), ECOG ?2, with metastatic leiomyosarcomas (LMS) after first-line doxorubicin chemotherapy failure were eligible. Pts were treated with G 1000 mg/m2 on days 1 and 8 of each 21 days (maximum eight cycles), in combination with oral daily P (800 mg), until disease progression/toxicity. 9-month progression-free survival (PFS) rate was the primary endpoint. Inacceptable and promising 9-month PFS rates were defined, in the intent-to-treat population, as 32% and 44%.106 pts were included with a mean age of 59.8 years and an ECOG 0 in 63.5%; the primary tumour site was uterus in 61%. Pts were treated with P + G for a median of 3.8 mo, and P for a median of 4.2 mo. The 9-month PFS rate was 32.1% (95% CI 23.1-41.1). After a median follow-up of 14.2 months, the PFS was 6.5 months (95% CI 5.6-8.2), and the overall survival was 22.4 months (95% CI 16.9-26.5). The best response was 23.8%. The most frequent reported grade 3-4 adverse events were haematological.LMS03 failed to show that second-line therapy, with gemcitabine combined with pazopanib, followed by pazopanib alone, was beneficial for advanced LMS patients. Eudract N°2011-001308-36 and NCT01442662.
MeSH: 
Adult|Aged|Aged, 80 and over|Antimetabolites, Antineoplastic|Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use|Deoxycytidine/analogs & derivatives/pharmacology/therapeutic use|Female|Humans|Leiomyosarcoma/drug therapy|Male|Middle Aged|Pyrimidines/pharmacology/therapeutic use|Sulfonamides/pharmacology/therapeutic use
Mots clés auteurs: 
/Chemotherapy/Leiomyosarcoma/Maintenance therapy/Metastatic disease/Pazopanib
DOI: 
10.1016/j.ejca.2019.10.028
PMID: 
31835236