Leiomyosarcoma

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Section editor
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 Elizabeth J. Davis, MD
Vanderbilt University
Nashville, TN, USA

Note: these are regimens tested in subtype-specific populations, please see the main soft tissue sarcoma page for other regimens.
For placebo or observational studies in this condition, please visit this page.

9 regimens on this page
15 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

Advanced or metastatic disease, first-line

Docetaxel & Gemcitabine

Regimen variant #1, 60/675

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hensley et al. 2015 (GOG-250) 2009-2013 Phase 3 (C) DG & Bevacizumab Did not meet primary endpoint of PFS

Note: This regimen was intended for patients who received prior radiation.

Chemotherapy

21-day cycles


Regimen variant #2, 75/675

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hensley et al. 2002 NR Phase 2
Seddon et al. 2017 (GeDDiS) 2010-2014 Phase 3 (E-switch-ic) Doxorubicin Did not meet primary endpoint of alive and progression free at 24 weeks

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

Chemotherapy

Supportive therapy

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after docetaxel)
  • 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/μL 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 Dates of enrollment Evidence Comparator Comparative Efficacy
Hensley et al. 2015 (GOG-250) 2009-2013 Phase 3 (C) DG & Bevacizumab Did not meet primary endpoint of PFS

Note: This regimen was intended for patients with no prior radiation.

Chemotherapy

21-day cycles


Regimen variant #4, 100/900

Study Dates of enrollment Evidence
Hensley et al. 2002 NR Phase 2
Hensley et al. 2008 (GOG 87L) 2003-2006 Phase 2

Note: This regimen was intended for patients with no prior radiation.

Chemotherapy

Supportive therapy

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after docetaxel)
  • 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/μL 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 dosing details in manuscript 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 dosing details in manuscript 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 NCT01012297
  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 ISRCTN07742377

Doxorubicin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Seddon et al. 2017 (GeDDiS) 2010-2014 Phase 3 (C) DG Did not meet primary endpoint of alive and progression free at 24 weeks
Pautier et al. 2022 (LMS-04) 2017-2019 Phase 3 (C) Doxorubicin & Trabectedin Inferior PFS

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 ISRCTN07742377
  2. LMS-04: Pautier P, Italiano A, Piperno-Neumann S, Chevreau C, Penel N, Firmin N, Boudou-Rouquette P, Bertucci F, Balleyguier C, Lebrun-Ly V, Ray-Coquard I, Kalbacher E, Bardet A, Bompas E, Collard O, Isambert N, Guillemet C, Rios M, Archambaud B, Duffaud F; French Sarcoma Group. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2022 Aug;23(8):1044-1054. Epub 2022 Jul 11. link to original article contains dosing details in abstract PubMed NCT02997358

Doxorubicin & Trabectedin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pautier et al. 2022 (LMS-04) 2017-2019 Phase 3 (E-esc) Doxorubicin Superior PFS (primary endpoint)
Median PFS: 12.2 vs 6.2 mo
(HR 0.41, 95% CI 0.29-0.58)

Chemotherapy

21-day cycles

References

  1. LMS-04: Pautier P, Italiano A, Piperno-Neumann S, Chevreau C, Penel N, Firmin N, Boudou-Rouquette P, Bertucci F, Balleyguier C, Lebrun-Ly V, Ray-Coquard I, Kalbacher E, Bardet A, Bompas E, Collard O, Isambert N, Guillemet C, Rios M, Archambaud B, Duffaud F; French Sarcoma Group. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2022 Aug;23(8):1044-1054. Epub 2022 Jul 11. link to original article contains dosing details in abstract PubMed NCT02997358

Advanced or metastatic disease, subsequent lines of therapy

Dacarbazine monotherapy

Regimen variant #1, 850 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (C) Eribulin Did not meet primary endpoint of OS1

1Reported efficacy is based on the 2019 subgroup analysis.

Chemotherapy

21-day cycles


Regimen variant #2, 1000 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Demetri et al. 2015 (ET743-SAR-3007) 2011-2013 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (C) Eribulin Did not meet primary endpoint of OS1

1Reported efficacy for E7389-G000-309 is based on the 2019 subgroup analysis.
Note: this is listed as a "starting dose" in Demetri et al. 2015, but no adjustment instructions were provided in the manuscript.

Chemotherapy

21-day cycles


Regimen variant #3, 1200 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (C) Eribulin Did not meet primary endpoint of OS1

1Reported efficacy is based on the 2019 subgroup analysis.

Chemotherapy

Supportive therapy

  • 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 dosing details in manuscript link to PMC article PubMed NCT01343277
    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. link to original article link to PMC article 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 link to PMC 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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
García-Del-Muro et al. 2011 2005-2008 Randomized Phase 2, fewer than 20 pts in this subgroup (E-esc) Dacarbazine Superior OS (secondary endpoint)
Median OS: 16.8 vs 8.2 mo
(HR 0.56, 95% CI 0.36-0.90)

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 dosing details in manuscript PubMed EudraCT 2005-001709-24

Docetaxel & Gemcitabine

Regimen variant #1, 75/675

Study Dates of enrollment Evidence
Hensley et al. 2002 NR Phase 2

Note: This regimen was intended for patients who received prior radiation.

Chemotherapy

Supportive therapy

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after docetaxel)
  • 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/μL 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 #2, 100/900

Study Dates of enrollment Evidence
Hensley et al. 2002 NR Phase 2

Note: This regimen was intended for patients with no prior radiation.

Chemotherapy

Supportive therapy

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after docetaxel)
  • 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/μL on two separate measurements
    • Pegfilgrastim (Neulasta) 6 mg SC once on either day 9 or 10

21-day cycle for 6 to 8 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 dosing details in manuscript PubMed

Eribulin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (E-switch-ic) Dacarbazine Did not meet primary endpoint of OS1

1Reported 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 contains dosing details in abstract 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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Mir et al. 2016 (REGOSARC) 2013-08-05 to 2014-11-26 Randomized Phase 2 (E-esc) Placebo Superior PFS1 (primary endpoint)
Median PFS: 3.7 vs 1.8 mo
(HR 0.46, 95% CI 0.46-0.80)

1Reported efficacy is for the leiomyosarcoma cohort.

Targeted therapy

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 dosing details in abstract PubMed NCT01900743

Trabectedin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Demetri et al. 2009 2003-NR Randomized Phase 2 (E-switch-ic) Trabectedin; alternate schedule Seems to have superior TTP (primary endpoint)
Demetri et al. 2015 (ET743-SAR-3007) 2011-2013 Phase 3 (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 therapy

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 dosing details in abstract 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 dosing details in manuscript link to PMC article PubMed NCT01343277
    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. link to original article link to PMC article 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 link to PMC article PubMed
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