A single-arm multicentre phase II trial of doxorubicin in combination with trabectedin in the first-line treatment for leiomyosarcoma with long-term follow-up and impact of cytoreductive surgery

Autor: Anne Floquet, Frédéric Selle, Esma Saada-Bouzid, Benjamin Lacas, Olivier Collard, Christine Chevreau, François Bertucci, Patricia Pautier, C. Delcambre, Maud Toulmonde, P Soulier, Didier Cupissol, Valerie Lebrun-Ly, Florence Duffaud, Emmanuelle Bompas, C. Guillemet, Jérôme Alexandre, N. Isambert, A. Le Cesne, Nicolas Penel, Sophie Piperno-Neumann
Přispěvatelé: Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Bergonié [Bordeaux], UNICANCER, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Dupuytren [CHU Limoges], CRLCC Paul Papin, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital de la Timone [CHU - APHM] (TIMONE), Bertucci, François, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: ESMO Open
ESMO Open, 2021, 6 (4), pp.100209. ⟨10.1016/j.esmoop.2021.100209⟩
ISSN: 2059-7029
DOI: 10.1016/j.esmoop.2021.100209⟩
Popis: Background Uterine leiomyosarcomas (U-LMSs) and soft tissue leiomyosarcomas (ST-LMSs) are rare tumours with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with manageable toxicity. Herein, we report the updated and long-term results of progression-free survival (PFS) and overall survival (OS). Patients and methods Patients received 60 mg/m2 intravenous doxorubicin followed by trabectedin 1.1 mg/m2 as a 3-h infusion on day 1 and pegfilgrastim on day 2, every 3 weeks, up to six cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. Results One-hundred and eight patients were enrolled, mainly with metastatic disease (85%), and 20 patients (18.5%) had surgical resection of metastases after chemotherapy. With a median follow-up of 7.2 years [95% confidence interval (CI) 6.9-8.2 years], the median PFS was 10.1 months (95% CI 8.5-12.6 months) in the whole population, and 8.3 months (95% CI 7.4-10.3 months) and 12.9 months (95% CI 9.2-14.1 months) for U-LMSs and ST-LMSs, respectively. The median OS was 34.4 months (95% CI 26.9-42.7 months), 27.5 months (95% CI 17.9-38.2 months), and 38.7 months (95% CI 31.0-52.9 months) for the whole population, U-LMSs, and ST-LMSs, respectively. The median OS of the patients with resected metastases was not reached versus 31.6 months in the overall population without surgery (95% CI 23.9-35.4 months). Conclusions These updated results confirm the impressive efficiency of the doxorubicin plus trabectedin combination given in first-line therapy for patients with locally advanced/metastatic LMS in terms of PFS and OS. Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing the doxorubicin plus trabectedin combination versus doxorubicin alone in first-line therapy in metastatic LMSs, are pending.
Highlights • Long-term results on PFS and OS of doxorubicin and trabectedin in first-line treatment for advanced leiomyosarcoma. • The update confirms the impressive efficiency of the doxo+trab in terms of PFS and OS. • Results of a randomized phase-III study comparing dox+trab combination versus doxo alone in first-line therapy in metastatic LMS are pending.
Databáze: OpenAIRE
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