Table 5.
Clinical results targeting uterine leiomyosarcoma.
| Drug(s) and Clinical Trial Identifier | Study Design | Indication | Grade 3 and 4 Toxicities | Efficacy | Year | Refs. |
|---|---|---|---|---|---|---|
| Intensified doxorubicin plus ifosfamide NCT00061984 EORTC 62012 (complete) |
EORTC phase 3 randomized study evaluating OS of intensified doxorubicin plus ifosfamide vs. doxorubicin use as first-line treatment | locally advanced, unresectable, or metastatic high-grade soft tissue sarcoma and no prior systemic cytotoxic treatment (but adjuvant chemo allowed) | ebrile neutropenia (46%) leukopenia (43%) neutropenia (42%) anemia (35%) thrombocytopenia (33%) |
mPFS: 7.4 mo vs. 4.6 mo HR 0.74 p = 0.003 mOS: 14.3 mo vs. 12.8 mo HR 0.83 p = 0.076 ORR: 26% (60/227) |
2014 | [193] |
| Fixed-dose rate gemcitabine plus docetaxel | GOG phase 2 study evaluating PFS of fixed-dose rate gemcitabine plus docetaxel use as first-line treatment | metastatic unresectable uLMS and no prior systemic cytotoxic treatment | anemia (23.8%) thrombocytopenia (19%) neutropenia (16.7%) fatigue (16.7%) metabolic toxicities (16.7%) leukopenia (14.3%) GI toxicity (14.3%) |
mPFS: 4.4 mo mOS: 16.1+ mo ORR: 35.7% (15/42) |
2008 | [194] |
| Doxorubicin plus trabectedin NCT02997358 (Complete) |
randomized phase 3 study evaluating PFS of doxorubicin and trabectedin use vs. doxorubicin alone as first-line treatment | metastatic or relapsed unresectable LMS without prior systemic treatment | neutropenia (80%) leukopenia (75%) thrombocytopenia (57%) ALT increase (42%) anemia (31%) renal creatinine clearance decreases (31%) febrile neutropenia (28%) fatigue (11%) |
mPFS: 12.2 mo vs. 6.2 mo HR 0.41, p < 0.0001 ORR: 36% (27/74) vs. 13% (10/74) uLMS ORR: 36% (12/33) vs. 15% (5/34) |
2022 | [196] |
| Fixed-dose rate gemcitabine with docetaxel | GOG phase 2 study evaluating efficacy of fixed-dose gemcitabine with docetaxel | advanced or recurrent uLMS progressed after at least one prior line excluding gemcitabine or docetaxel use | thrombocytopenia (39.5%) anemia (25%) leukopenia (23%) neutropenia (20.8%) |
mPFS: 6.7+ mo mOS: 14.7 mo ORR: 27% (13/48) |
2008 | [194] |
| Trabectedin NCT01343277 (Complete) |
randomized phase 3 study evaluating OS of trabectedin use compared to dacarbazine use | advanced liposarcoma or LMS after at least two prior lines with at least one containing anthracycline | neutropenia (37%) ALT elevation (26%) thrombocytopenia (17%) anemia (14%) AST elevation (13%) |
mPFS: 4.2 mo vs. 1.5 mo HR 0.55, p < 0.001 mOS: 12.4 mo vs. 12.9 mo HR 0.87, p = 0.37 ORR: 9.9% (34/345) vs. 6.9% (12/173), p = 0.33 |
2016 | [200] |
| Pazopanib NCT00753688 (Complete) |
randomized phase 3 study evaluating PFS of pazopanib use compared to placebo | progressive metastatic soft tissue sarcoma with at least one prior line containing anthracycline, up to four prior lines | fatigue (14%) hypertension (7%) anorexia (6%) |
mPFS: 4.6 mo vs. 1.6 mo HR 0.31, p < 0.0001 mOS: 12.5 mo vs. 10.7 mo HR 0.86, p = 0.2514 ORR: 14/246 (6%) vs. 0/123 (0%) |
2012 | [201] |
| Eribulin NCT01327885 (Complete) |
randomized phase 3 study evaluating OS of eribulin compared to dacarbazine use | Intermediate- or high-grade advanced-stage liposarcoma or LMS with at least two prior lines including anthracycline use | neutropenia (35%) leukopenia (10%) anemia (7%) |
mPFS: 2.2 mo vs. 2.6 mo HR 1.07, p = 0.58 mOS: 13.5 mo vs. 11.5 mo HR 0.77, p = 0.0169 LMS subgroup mPFS: 1.4 vs. 2.6 mo, HR 1.57 mOS: 12.7 mo vs. 13.0 mo HR 0.93 ORR 9/228 (4%) vs. 11/224 (5%) |
2016 | [202] |
| Olaparib and temozolomide NCT03880019 (Complete) |
phase 2 single-arm open-label study evaluating olaparib and temozolomide | advanced and unresectable or metastatic uterine LMS patients | neutropenia (75%) thrombocytopenia (32%) leukopenia (22%) |
mPFS 11.2 mo in HR-deficient patients vs. mPFS 5.4 mo in HR-proficient patients p = 0.05 ORR 6/22 (27%) |
2023 | [205] |
| Olaparib and temozolomide NCT05432791 (Active) |
randomized phase 2/3 study evaluating PFS and OS of olaparib plus temozolomide compared to investigator’s choice | advanced and unresectable or metastatic uLMS patients who received two or more prior lines including anthracycline use | NA | NA | ongoing | NA |
| Lurbinectedin and doxorubicin NCT05099666 (Active) |
phase Ib/2 study exploring safety and efficacy of lurbinectedin and doxorubicin | Phase Ib: advanced or metastatic soft-tissue sarcoma with no more than two prior lines, and no prior anthracycline or trabectedin use. Phase 2: advanced or metastatic LMS with no more than one prior line and no prior anthracycline or trabectedin use. |
NA | NA | ongoing | NA |
| Gemcitabine, dacarbazine, and HIPEC NCT04727242 (Active) |
phase 2 study evaluating the use of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with gemcitabine followed by systemic adjuvant chemotherapy with dacarbazine | locally recurrent uLMS without extra-abdominal disease, and no prior gemcitabine or dacarbazine use | NA | NA | ongoing | NA |
Abbreviations: NA: not available; PFS: progression-free survival; OS: overall survival.