P Pautier1, N Penel2, I Ray-Coquard3, A Italiano4, E Bompas5, C Delcambre6, J-O Bay7, F Bertucci8, J Delaye9, C Chevreau10, D Cupissol11, L Bozec12, J-C Eymard13, E Saada14, N Isambert15, C Guillemet16, M Rios17, S Piperno-Neumann18, G Chenuc19, F Duffaud20. 1. Gustave Roussy, Villejuif, France. Electronic address: patricia.pautier@gustaveroussy.fr. 2. Centre Oscar-Lambret & Lille University, Lille, France. 3. Centre Léon-Bérard & University Claude Bernard Lyon Est, Lyon, France. 4. Institut Bergonié, Bordeaux, France. 5. Institut de Cancérologie de L'Ouest, Angers-Nantes, France. 6. Centre François-Baclesse, Caen, France. 7. Centre Jean-Perrin, Clermont-Ferrand, France. 8. Institut Paoli-Calmettes, Marseille, France. 9. R&D Unicancer, Paris, France. 10. Institut Claudius-Regaud, Toulouse, France. 11. Institut Du Cancer, Montpellier, France. 12. Institut Curie, Hôpital René-Huguenin, Saint-Cloud, France. 13. Institut Jean-Godinot, Reims, France. 14. Centre Antoine-Lacassagne, Nice, France. 15. Centre Georges-François-Leclerc, Dijon, France. 16. Centre Henri-Becquerel, Rouen, France. 17. Centre Alexis-Vautrin, Vandoeuvre-les-Nancy, France. 18. Institut Curie, Paris, France. 19. Société Capionis, Paris, France. 20. CHU La Timone, Marseille, France.
Abstract
BACKGROUND: 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 AND METHODS: 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%. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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 AND METHODS: 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%. RESULTS: 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. CONCLUSIONS: LMS03 failed to show that second-line therapy, with gemcitabine combined with pazopanib, followed by pazopanib alone, was beneficial for advanced LMSpatients. Eudract N°2011-001308-36 and NCT01442662.
Authors: E F Nassif; J-Y Blay; C Massard; A Dufresne; M Brahmi; P Cassier; I Ray-Coquard; P Pautier; A Leary; M-P Sunyach; R Bahleda; A Levy; C Le Pechoux; C Honoré; O Mir; A Le Cesne Journal: ESMO Open Date: 2022-03-05