Dosing and uses of Lartruvo (olaratumab)
Adult dosage forms and strengths
IV solution
- 500mg/50mL vial (10mg/mL)
Soft Tissue Sarcoma
Indicated, in combination with doxorubicin, for soft-tissue sarcomas with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery
15 mg/kg IV infused over 1 hr on Days 1 and 8 of each 21-day cycle
Administer with doxorubicin for the first 8 cycles
Continue until disease progression or unacceptable toxicity
See Administration for preparation and premedication
Dosage modifications
Infusion-related reactions
- Grade 3 or 4: Permanently discontinue
- Grade 1 or 2: Interrupt infusion; after resolution, resume IV infusion at 50% of the initial rate
Neutropenia
- Grade 4 neutropenia >1 wk or neutropenic fever/infection: Discontinue until the ANC is ≥1000 /microliter and then permanently reduce dose to 12 mg/kg
Hepatic impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Unknown
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment required
- Severe (CrCl 15-29 mL/min): Unknown
Dosing Considerations
Approved under accelerated approval; continued approval may be contingent upon verification and description of clinical benefit in the confirmatory triaL
Pediatric dosage forms and strengths
Safety and efficacy not established
Lartruvo (olaratumab) adverse (side) effects
>10%
Lymphopenia, all grades (77%)
Nausea, all grades (73%)
Fatigue, all grades (69%)
Neutropenia, all grades (65%)
Musculoskeletal pain, all grades (64%)
Thrombocytopenia, all grades (63%)
Mucositis, all grades (53%)
Alopecia, all grades (52%)
Hyperglycemia, all grades (52%)
Neutropenia, grade 3-4 (48%)
Vomiting, all grades (45%)
Lymphopenia, grade 3-4 (44%)
Diarrhea, all grades (34%)
Increased aPTT, all grades (33%)
Decreased appetite, all grades (31%)
Abdominal pain, all grades (23%)
Neuropathy, all grades (22%)
Hypokalemia, all grades (21%)
Hypophosphatemia, all grades (21%)
Headache, all grades (20%)
Increased alkaline phosphatase, all grades (16%)
Hypomagnesemia, all grades (16%)
Infusion-related reactions, all grades (13%)
Anxiety, all grades (11%)
Dry eyes, all grades (11%)
1-10%
Fatigue, grade 3-4 (9%)
Musculoskeletal pain, grade 3-4 (8%)
Hypokalemia, grade 3-4 (8%)
Thrombocytopenia, grade 3-4 (6%)
Increases aPTT, grade 3-4 (5%)
Hypophosphatemia, grade 3-4 (5%)
Abdominal pain, grade 3-4 (3%)
Diarrhea, grade 3-4 (3%)
Mucositis, grade 3-4 (3%)
Infusion-related reactions, grade 3-4 (3%)
Nausea, grade 3-4 (2%)
Decreased appetite, grade 3-4 (2%)
Hyperglycemia, grade 3-4 (2%)
Warnings
Contraindications
None
Cautions
Infusion-related reactions
- May cause infusion-related reactions; premedicate before first dose (see Administration)
- Infusion-related reactions may require permanent discontinuation or interruption of infusion (see Dosage modifications)
- Monitor during and following infusions for reactions
- Administer in a setting with available resuscitation equipment
Embryo-fetal toxicity
- Based on animal data and its mechanism of action, can cause fetal harm when administered to a pregnant woman
- Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose
- Advise women to inform their healthcare provider of known or suspected pregnancy
- Also see Pregnancy
Pregnancy
Pregnancy
Based on animal data and its mechanism of action, can cause fetal harm
There are no available data on use in pregnant women
No animal studies using olaratumab have been conducted to evaluate its effect on female reproduction and embryo-fetal development
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose
Infertility
- Males: Based on animal models, may impair male fertility
Lactation
Unknown if distributed in human breast milk
Advise women not to breast feed during treatment and for 3 months following the last dose
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Lartruvo (olaratumab)
Mechanism of action
Recombinant human IgG1 monoclonal blocking antibody that binds specifically to human platelet-derived growth factor receptor-alpha (PDGFR-alpha)
PDGFR-alpha is a tyrosine kinase receptor expressed on cells of mesenchymal origin; signaling through this receptor plays a role in cell growth, chemotaxis, and mesenchymal stem cell differentiation
PDGFR-alpha has also been detected on some tumor and stromal cells, including sarcomas, where signaling can contribute to cancer cell proliferation, metastasis, and maintenance of the tumor microenvironment
The interaction between olaratumab and PDGFR-alpha prevents binding of the receptor by the PDGF-AA and -BB ligands as well as PDGF-AA, -BB, and -CC-induced receptor activation and downstream PDGFR-alpha pathway signaling
Distribution
Vd: 7.7 L (16%)
Elimination
Half-life: ~11 days (range 6-24 days)
Clearance: 0.56 L/day (33%)
Administration
IV Compatibilities
0.9% NaCL
IV Incompatibilities
Dextrose-containing solutions
Electrolyte-containing solutions (eg, Ringers Lactate)
IV Preparation
Solution in unopened vial should appear clear to slightly opalescent, colorless to slightly yellow
Inspect vial contents for particulate matter and discoloration prior to dilution; discard if particulate matter or discolorations is identified
Withdraw calculated dose and further dilute with 0.9% NaCl to a final volume of 250 mL for IV infusion; do not use dextrose-containing or other solutions
Gently invert but do not shake
Do not freeze the diluted solution
Store the diluted solution for up to 24 hr under refrigeration at 2-8°C (36-46°F) and for up to an additional 4 hr at room temperature (<25°C [77°F])
Storage times include the duration of infusion; if refrigerated, allow the diluted solution to come to room temperature before administration
Discard vial with any unused portion
IV Administration
Premedication
- Premedicate with diphenhydramine (25-50 mg IV) and dexamethasone (10-20 mg IV) before olaratumab dose on Day 1 of cycle 1
Intravenous infusion
- Do not administer as IV push or bolus
- Do not infuse with electrolytes or other medications through the same IV line
- Visually inspect the diluted solution for particulate matter and discoloration prior to administration; if particulate matter or discolorations is identified, discard the solution
- Administer diluted solution as an IV infusion over 1 hr
- Flush the line with 0.9% NaCl at end of infusion
Storage
Unopened viaL
- Preservative-free solution
- Refrigerate at 2-8°C (36-46°F) until time of use
- Keep the vial in the outer carton to protect from light
- Do not freeze
- Do not shake vial
Diluted solution
- Refrigerate for up to 24 hr at 2-8°C (36-46°F) and for up to an additional 4 hr at room temperature (<25°C [77°F])
- Do not freeze
- Do not shake diluted solution
