Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma

Shreyaskumar Patel, Margaret von Mehren, Damon R. Reed, Pamela Kaiser, John Charlson, Christopher Ryan, Daniel Rushing, Michael Livingston, Arun Singh, Rahul Seth, Charles Forscher, Gina D'Amato, Sant P. Chawla, Sharon McCarthy, George Wang, Trilok Parekh, Roland Knoblauch, Martee L. Hensley, Robert G. Maki, George D. Demetri

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    Abstract

    Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. Results: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P =.49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively). Conclusion: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin.

    Original languageEnglish (US)
    Pages (from-to)2610-2620
    Number of pages11
    JournalCancer
    Volume125
    Issue number15
    DOIs
    StatePublished - Aug 1 2019

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    trabectedin
    Liposarcoma
    Dacarbazine
    Leiomyosarcoma
    Histology
    Survival
    Survival Analysis
    Therapeutics

    Keywords

    • dacarbazine
    • leiomyosarcoma
    • liposarcoma
    • soft tissue sarcoma
    • trabectedin

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. / Patel, Shreyaskumar; von Mehren, Margaret; Reed, Damon R.; Kaiser, Pamela; Charlson, John; Ryan, Christopher; Rushing, Daniel; Livingston, Michael; Singh, Arun; Seth, Rahul; Forscher, Charles; D'Amato, Gina; Chawla, Sant P.; McCarthy, Sharon; Wang, George; Parekh, Trilok; Knoblauch, Roland; Hensley, Martee L.; Maki, Robert G.; Demetri, George D.

    In: Cancer, Vol. 125, No. 15, 01.08.2019, p. 2610-2620.

    Research output: Contribution to journalArticle

    Patel, S, von Mehren, M, Reed, DR, Kaiser, P, Charlson, J, Ryan, C, Rushing, D, Livingston, M, Singh, A, Seth, R, Forscher, C, D'Amato, G, Chawla, SP, McCarthy, S, Wang, G, Parekh, T, Knoblauch, R, Hensley, ML, Maki, RG & Demetri, GD 2019, 'Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma', Cancer, vol. 125, no. 15, pp. 2610-2620. https://doi.org/10.1002/cncr.32117
    Patel, Shreyaskumar ; von Mehren, Margaret ; Reed, Damon R. ; Kaiser, Pamela ; Charlson, John ; Ryan, Christopher ; Rushing, Daniel ; Livingston, Michael ; Singh, Arun ; Seth, Rahul ; Forscher, Charles ; D'Amato, Gina ; Chawla, Sant P. ; McCarthy, Sharon ; Wang, George ; Parekh, Trilok ; Knoblauch, Roland ; Hensley, Martee L. ; Maki, Robert G. ; Demetri, George D. / Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. In: Cancer. 2019 ; Vol. 125, No. 15. pp. 2610-2620.
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    abstract = "Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. Results: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73{\%}) with LMS and 154 (27{\%}) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42{\%} vs 22{\%}). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43{\%} vs 24{\%}; LPS, 40{\%} vs 16{\%}). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P =.49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71{\%} vs 69{\%}, respectively). Conclusion: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin.",
    keywords = "dacarbazine, leiomyosarcoma, liposarcoma, soft tissue sarcoma, trabectedin",
    author = "Shreyaskumar Patel and {von Mehren}, Margaret and Reed, {Damon R.} and Pamela Kaiser and John Charlson and Christopher Ryan and Daniel Rushing and Michael Livingston and Arun Singh and Rahul Seth and Charles Forscher and Gina D'Amato and Chawla, {Sant P.} and Sharon McCarthy and George Wang and Trilok Parekh and Roland Knoblauch and Hensley, {Martee L.} and Maki, {Robert G.} and Demetri, {George D.}",
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    TY - JOUR

    T1 - Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma

    AU - Patel, Shreyaskumar

    AU - von Mehren, Margaret

    AU - Reed, Damon R.

    AU - Kaiser, Pamela

    AU - Charlson, John

    AU - Ryan, Christopher

    AU - Rushing, Daniel

    AU - Livingston, Michael

    AU - Singh, Arun

    AU - Seth, Rahul

    AU - Forscher, Charles

    AU - D'Amato, Gina

    AU - Chawla, Sant P.

    AU - McCarthy, Sharon

    AU - Wang, George

    AU - Parekh, Trilok

    AU - Knoblauch, Roland

    AU - Hensley, Martee L.

    AU - Maki, Robert G.

    AU - Demetri, George D.

    PY - 2019/8/1

    Y1 - 2019/8/1

    N2 - Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. Results: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P =.49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively). Conclusion: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin.

    AB - Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. Results: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P =.49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively). Conclusion: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin.

    KW - dacarbazine

    KW - leiomyosarcoma

    KW - liposarcoma

    KW - soft tissue sarcoma

    KW - trabectedin

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