Class: Antineoplastic Agents
- Platelet-derived Growth Factor Receptor (PDGFR) Alpha Inhibitors
- PDGF Receptor-α Inhibitors
- PDGFR-α Inhibitors
Chemical Name: Disulfide with human monoclonal 3G3 κ-chain, anti-(human platelet-derived growth factor receptor α) (human monoclonal 3G3 γ-chain), immunoglobulin G1, dimer
Molecular Formula: C6554H10076N1736O2048S40
CAS Number: 1024603-93-7
Notice: On April 25, 2019, Lilly announced a worldwide withdrawal of olaratumab (Lartruvo) prompted by the failure of a phase 3 confirmatory study (ANNOUNCE) to verify clinical benefit of olaratumab in patients with locally advanced or metastatic soft tissue sarcoma.
Preliminary results from the ANNOUNCE study demonstrated no difference in overall survival in patients receiving olaratumab in combination with doxorubicin compared with those receiving doxorubicin alone.
Therapy may be continued only in patients currently receiving olaratumab therapy following consultation with their healthcare provider; do not initiate therapy in new patients outside of a controlled clinical trial. Contact the manufacturer at 877-285-4559 for information on the olaratumab expanded access program.
Antineoplastic agent; recombinant human IgG1 monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFR-α).
Uses for Olaratumab
Soft Tissue Sarcoma
Used in combination with doxorubicin for the treatment of soft tissue sarcoma that is not amenable to curative treatment with surgery or radiation therapy; patients must have a histologic subtype for which an anthracycline-containing regimen is appropriate (designated an orphan drug by FDA for treatment of this cancer ).
Accelerated approval was based on progression-free and overall survival. Continued approval was contingent on verification and description of clinical benefit in confirmatory studies.
Olaratumab Dosage and Administration
Consult respective manufacturers' labelings for information on dosage and method of administration of other antineoplastic agents used in combination regimens.
Administer in setting where resuscitation equipment is readily available.
Premedication for Infusion-related Reactions
Administer diphenhydramine hydrochloride 25–50 mg IV and dexamethasone phosphate 10–20 mg IV before olaratumab infusion on day 1 of cycle 1.
Available only through an expanded access program. Consult manufacturer (Lilly) at 877-285-4559 for specific information. (See Special Alerts.)
For solution compatibility information, see Compatibility under Stability.
Administer by IV infusion. Do not administer by rapid IV injection (e.g., IV push or bolus).
Do not administer with any other drug or electrolytes simultaneously in the same IV line.
Flush IV line with 0.9% sodium chloride injection after olaratumab administration.
Must be diluted prior to IV infusion.
Do not shake vial.
Withdraw appropriate volume of olaratumab injection concentrate from vial labeled as containing 10 mg/mL and dilute in 0.9% sodium chloride to yield a final volume of 250 mL.
Mix by gentle inversion; do not shake.
Do not dilute in dextrose-containing solutions or any other solutions.
Discard any partially used vials.
Rate of Administration
Administer by IV infusion over 60 minutes.
Soft Tissue Sarcoma
15 mg/kg on days 1 and 8 of each 21-day cycle; doxorubicin also is administered during cycles 1–8.
Continue olaratumab therapy until disease progression or unacceptable toxicity occurs.
Dosage Modification for Toxicity
If grade 1 or 2 infusion-related reactions occur, interrupt the infusion; upon resolution, may resume the infusion but reduce infusion rate by 50%. (See Infusion-related Effects under Cautions.)
If grade 3 or 4 infusion-related reactions occur, permanently discontinue olaratumab therapy.
If febrile neutropenia, neutropenic infection, or prolonged grade 4 neutropenia (lasting >1 week) occurs, withhold olaratumab therapy until ANC ≥1000/mm3; upon resumption, permanently reduce dosage to 12 mg/kg.
No specific dosage recommendations at this time. (See Hepatic Impairment under Cautions.)
No specific dosage recommendations at this time. (See Renal Impairment under Cautions.)
No specific dosage recommendations. (See Geriatric Use under Cautions.)
Cautions for Olaratumab
No known contraindications.
Infusion-related reactions (e.g., flushing, dyspnea, bronchospasm, fever/chills, severe hypotension, anaphylactic shock, cardiac arrest), sometimes fatal, reported; generally occur during first 2 cycles. Frequency of infusion-related reactions similar regardless of administration of premedication. Grade 1 or 2 infusion-related reactions recurred in 12 of 59 patients (20%) following resumption of infusion.
Monitor patients for manifestations of infusion reactions during and following olaratumab infusion in a setting where resuscitation equipment is readily available.
Premedicate with diphenhydramine and dexamethasone prior to first dose of olaratumab during cycle 1. (See Premedication for Infusion-related Reactions under Dosage and Administration.) If infusion-related reactions occur, temporary interruption followed by reduction in the infusion rate or permanent drug discontinuance may be required. (See Infusion-related Effects under Dosage and Administration.)
When used in combination with doxorubicin, consider cautions, precautions, and contraindications of doxorubicin.
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm.
Avoid pregnancy during therapy. Women of childbearing potential should use an effective contraceptive method while receiving olaratumab and for 3 months after the drug is discontinued. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.
Antibodies to olaratumab, including neutralizing antibodies to the drug, reported.
Impairment of Fertility
May impair male fertility.
May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether distributed into human milk. Discontinue nursing during therapy and for 3 months after drug discontinuance
Effects of the drug on nursing infants or on human milk production are unknown.
Safety and efficacy not established.
Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.
Pharmacokinetics not affected by mild to moderate hepatic impairment (total bilirubin concentration at or below ULN with AST concentration exceeding ULN or total bilirubin concentration above ULN, but not >3 times the ULN, with any AST concentration).
Not studied in patients with severe hepatic impairment (total bilirubin concentration >3 times the ULN with any AST concentration).
Pharmacokinetics not affected by mild to moderate renal impairment (Clcr 30–89 mL/minute).
Not studied in patients with severe renal impairment (Clcr 15–29 mL/minute).
Common Adverse Effects
Lymphopenia, nausea, fatigue, neutropenia, musculoskeletal pain, thrombocytopenia, mucositis, alopecia, hyperglycemia, vomiting, leukopenia, diarrhea, increased aPTT, decreased appetite, abdominal pain, pyrexia, neuropathy, hypokalemia, hypophosphatemia, headache, increased alkaline phosphatase concentrations, hypomagnesemia, peripheral edema, infusion-related reactions (including hypersensitivity and angioedema), anxiety, dry eyes.
Interactions for Olaratumab
No substantial effect on systemic exposure to either drug
Steady-state concentrations are achieved during cycle 3 following administration of olaratumab 15 mg/kg IV on days 1 and 8 along with doxorubicin hydrochloride 75 mg/m2 IV on day 1 of each 21-day cycle.
Approximately 11 days.
Mild to moderate hepatic impairment: Pharmacokinetics not affected.
Severe hepatic impairment: Not studied.
Mild to moderate renal impairment: Pharmacokinetics not affected.
Severe renal impairment: Not studied.
Age (over range of 22–85 years), gender, and race do not substantially affect pharmacokinetics. Clearance increases with increasing body weight.
2–8°C in original carton to protect from light. Do not freeze or shake.
Diluted solution: 2–8°C for up to 24 hours followed by an additional 8 hours (including infusion time) at room temperature (<25°C). Do not freeze or shake.
For information on systemic interactions resulting from concomitant use, see Interactions.
Sodium chloride 0.9%
Dextrose 5% in water
A recombinant human IgG1 monoclonal antibody that binds specifically to PDGFR-α (a receptor tyrosine kinase expressed on cells of mesenchymal origin), resulting in inhibition of downstream signaling.
Antitumor activity against selected sarcoma cell lines demonstrated in vitro and in vivo.
Disrupts PDGFR-α signaling in tumor implant models.
Advice to Patients
Risk of infusion-related reactions; importance of reporting signs and symptoms of such reactions (e.g., flushing, dyspnea, bronchospasm, fever/chills).
Risk of fetal harm. Necessity of advising women of childbearing potential that they should use an effective method of contraception while receiving the drug and for 3 months after discontinuance of therapy. Importance of women informing clinicians if they are pregnant. If pregnancy occurs, advise of potential fetal risk.
Necessity of advising women to avoid breast-feeding during therapy and for 3 months after discontinuance of therapy.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Distribution of olaratumab is limited to certain patients through an expanded access program. (See Restricted Distribution under Dosage and Administration.)
For injection concentrate, for IV infusion
10 mg/mL (190 and 500 mg)
AHFS DI Essentials™. © Copyright 2021, Selected Revisions April 20, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.