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Leiomyosarcoma

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Elizabeth J. Davis, MD
Vanderbilt University
Nashville, TN

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Note: these are regimens tested in subtype-specific populations, please see the main soft tissue sarcoma page for other regimens.

6 regimens on this page
11 variants on this page


Contents

Advanced or metastatic disease, all lines of therapy

Dacarbazine monotherapy

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Regimen variant #1, 850 mg/m2

Study Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) Phase III (C) Eribulin Did not meet primary endpoint of OS (*)

Note: reported efficacy is based on the 2019 subgroup analysis.

Chemotherapy

21-day cycles

Regimen variant #2, 1000 mg/m2

Study Evidence Comparator Comparative Efficacy
Demetri et al. 2015 (ET743-SAR-3007) Phase III (C) Trabectedin Did not meet primary endpoint of OS
Schöffski et al. 2016 (E7389-G000-309) Phase III (C) Eribulin Did not meet primary endpoint of OS (*)

Note: this is listed as a "starting dose" in Demetri et al. 2015, but no adjustment instructions were provided in the manuscript. Reported efficacy for E7389-G000-309 is based on the 2019 subgroup analysis.

Chemotherapy

21-day cycles

Regimen variant #3, 1200 mg/m2

Study Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) Phase III (C) Eribulin Did not meet primary endpoint of OS (*)

Note: reported efficacy is based on the 2019 subgroup analysis.

Chemotherapy

Supportive medications

  • Buesa et al. 1991: Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.

21-day cycles

References

  1. ET743-SAR-3007: Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. link to original article contains verified protocol link to PMC article PubMed
    1. Subgroup analysis: Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. PubMed
    2. Update: Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, 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. 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. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. link to original article PubMed
  2. E7389-G000-309: Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. link to original article PubMed NCT01327885
    1. Subgroup analysis: Blay JY, Schöffski P, Bauer S, Krarup-Hansen A, Benson C, D'Adamo DR, Jia Y, Maki RG. Eribulin versus dacarbazine in patients with leiomyosarcoma: subgroup analysis from a phase 3, open-label, randomised study. Br J Cancer. 2019 May;120(11):1026-1032. Epub 2019 May 8. link to original article link to PMC article PubMed

Dacarbazine & Gemcitabine

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Regimen

Study Evidence Comparator Comparative Efficacy
García-Del-Muro et al. 2011 Randomized Phase II, <20 pts in this subgroup (E-esc) Dacarbazine Seems to have superior OS

Chemotherapy

14-day cycle for at least 12 cycles

References

  1. García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. link to original article contains verified protocol PubMed

Docetaxel & Gemcitabine

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Regimen variant #1, 60/675

Study Evidence Comparator Comparative Efficacy
Hensley et al. 2015 (GOG-250) Phase III (C) Docetaxel, Gemcitabine, Bevacizumab Did not meet primary endpoint of PFS

This regimen was intended for patients who received prior radiation.

Chemotherapy

21-day cycles

Regimen variant #2, 75/675

Study Evidence Comparator Comparative Efficacy
Hensley et al. 2002 Phase II
Seddon et al. 2017 (GeDDiS) Phase III (E-switch-ic) Doxorubicin Might have inferior PFS

In Hensley et al. 2002, this regimen was intended for patients who received prior radiation.

Chemotherapy

Supportive medications

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after Docetaxel (Taxotere))
  • Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
  • One of the following growth factors (varies depending on reference):
    • G-CSF (type not specified) 150 mcg/m2 (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
    • Pegfilgrastim (Neulasta) 6 mg SC once on either day 9 or 10

21-day cycle for 6 to 8 cycles

Regimen variant #3, 75/900

Study Evidence Comparator Comparative Efficacy
Hensley et al. 2015 (GOG-250) Phase III (C) Docetaxel, Gemcitabine, Bevacizumab Did not meet primary endpoint of PFS

This regimen was intended for patients with no prior radiation.

Chemotherapy

21-day cycles

Regimen variant #4, 100/900

Study Evidence
Hensley et al. 2002 Phase II
Hensley et al. 2008 (GOG 87L) Phase II

This regimen was intended for patients with no prior radiation.

Chemotherapy

Supportive medications

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after Docetaxel (Taxotere))
  • Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
  • One of the following growth factors (varies depending on reference):
    • G-CSF (type not specified) 150 mcg/m2 (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
    • Pegfilgrastim (Neulasta) 6 mg SC once on either day 9 or 10

21-day cycle for 6 to 8 cycles; Hensley et al. 2008 did not specify a maximum number of cycles

References

  1. Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. link to original article contains verified protocol PubMed
  2. GOG 87L: Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008 Jun;109(3):329-34. link to original article contains verified protocol link to PMC article PubMed
  3. GOG-250: Hensley ML, Miller A, O'Malley DM, Mannel RS, Behbakht K, Bakkum-Gamez JN, Michael H. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2015 Apr 1;33(10):1180-5. Epub 2015 Feb 23. link to original article link to PMC article PubMed
  4. GeDDiS: Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. link to original article link to PMC article PubMed

Eribulin monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) Phase III (E-switch-ic) Dacarbazine Did not meet primary endpoint of OS (*)

Note: reported efficacy is based on the 2019 subgroup analysis.

Chemotherapy

21-day cycles

References

  1. E7389-G000-309: Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. link to original article PubMed NCT01327885
    1. Subgroup analysis: Blay JY, Schöffski P, Bauer S, Krarup-Hansen A, Benson C, D'Adamo DR, Jia Y, Maki RG. Eribulin versus dacarbazine in patients with leiomyosarcoma: subgroup analysis from a phase 3, open-label, randomised study. Br J Cancer. 2019 May;120(11):1026-1032. Epub 2019 May 8. link to original article link to PMC article PubMed

Regorafenib monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Mir et al. 2016 (REGOSARC) Randomized Phase II (E-esc) Placebo Superior PFS

Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.

Chemotherapy

28-day cycles

References

  1. REGOSARC: Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. link to original article contains protocol PubMed

Trabectedin monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Demetri et al. 2009 2003-NR Randomized Phase II (E-switch-ic) Trabectedin; alternate schedule Seems to have superior TTP
Demetri et al. 2015 (ET743-SAR-3007) 2011-2015 Phase III (E-RT-switch-ic) Dacarbazine Did not meet primary endpoint of OS

Note: in Demetri et al. 2015, this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.

Chemotherapy

Supportive medications

21-day cycles

References

  1. Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. link to original article contains protocol PubMed
  2. ET743-SAR-3007: Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. link to original article contains verified protocol link to PMC article PubMed
    1. Subgroup analysis: Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. PubMed
    2. Update: Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, 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. 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. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. link to original article PubMed