Table 1.

Novel and Targeted Agents for the Treatment of Soft-Tissue Sarcomas

Drug Name	Indicated Sarcoma Histology	Dosing	Mechanism of Action	Adverse Events*	Additional Comments
Olaratumab (Lartruvo, Eli Lilly)35,38	Any histological subtype for which an anthracycline-containing regimen is appropriate	15 mg/kg IV days 1 and 8 every 21 days	Inhibits PDGFRα	Nausea, fatigue, neutropenia, mucositis, alopecia, vomiting, anemia, constipation, diarrhea, decreased appetite, pyrexia, abdominal pain, febrile neutropenia, cardiac dysfunction†	Premedicate with diphen-hydramine 25–50 mg IV and dexamethasone 10–20 mg IV on cycle 1, day 1 of treatment to prevent infusion reaction May cause fetal harm when administered in pregnancy
Trabectedin (Yondelis, Janssen)40,42	Leiomyosarcoma, liposarcoma	1.5 mg/m2 CIVI over 24 hours every 21 days	Alkylating agent, binds to minor groove of DNA	Nausea, decreased appetite, constipation, malaise, vomiting, anemia, myalgia, pyrexia, diarrhea, neutropenia, ALT increase, AST increase, thrombocytopenia, lymphopenia	Premedicate with dexamethasone 20 mg to prevent hepatotoxicity Vesicant, administer via central venous line Avoid concomitant administration with CYP3A4 inhibitors and inducers May cause fetal harm when administered in pregnancy
Eribulin (Halaven, Eisai)44,45	Liposarcoma	1.4 mg/m2 days 1 and 8 every 21 days	Nontaxane microtubule inhibitor	Neutropenia, fatigue, nausea, alopecia, constipation, pyrexia, anemia, asthenia, decreased appetite, peripheral neuropathy	May cause fetal harm when administered in pregnancy
Pazopanib (Votrient, Novartis)46,47	Leiomyosarcoma	800 mg orally daily	Inhibits VEGFR, PDGFR, FGFR, c-Kit	Fatigue, diarrhea, nausea, weight loss, hypertension, anorexia, hair hypopigmentation, vomiting, dysgeusia	Avoid concomitant administration with CYP3A4 inhibitors and inducers May cause fetal harm when administered in pregnancy Administer on an empty stomach at least 1 hour before or 2 hours after a meal
Regorafenib (Stivarga, Bayer Healthcare)48,49	Leiomyosarcoma, synovial sarcoma	160 mg orally daily for 3 weeks, then 1 week off	Inhibits c-Kit, VEGFR, PDGFR, RET, BRAF	Asthenia, pain, myalgia, anorexia, abdominal pain, diarrhea, mucositis, hand–foot syndrome, hypertension, dyspnea, hypophosphatemia	Avoid concomitant administration with CYP3A4 inhibitors and inducers May cause fetal harm when administered in pregnancy Administer with a low-fat breakfast

^*Common all-grade adverse events observed in > 20% of patients receiving drug in clinical trial.

^†All-grade adverse events observed in > 20% of patients receiving olaratumab/doxorubicin.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CIVI = continuous intravenous infusion; CYP3A4 = cytochrome P450 3A4; FGFR = fibroblast growth factor receptor; IV = intravenous; PDGFR = platelet-derived growth factor receptor; RET = rearranged during transfection; VEGFR = vascular endothelial growth factor receptor.