Version May 2024
Note: A confirmatory phase 3 randomized, blinded trial in patients with unresectable locally advanced or metastatic soft tissue sarcoma comparing olaratumab plus doxorubicin to placebo plus doxorubicin found no significant difference in overall survival due to the addition of olaratumab to doxorubicin (Tap 2020). Due to the trial results, the manufacturer has withdrawn olaratumab from the market.
Soft tissue sarcoma: IV: 15 mg/kg on days 1 and 8 every 3 weeks (in combination with doxorubicin) for 8 cycles; after 8 cycles are completed, continue olaratumab (as a single agent) until disease progression or unacceptable toxicity. Dexrazoxane was allowed on day 1 of cycles 5 to 8 to reduce the potential for doxorubicin-related cardiotoxicity (Tap 2016).
Premedications: On day 1 of cycle 1, premedicate with diphenhydramine (25 to 50 mg IV) and dexamethasone (10 to 20 mg IV) prior to olaratumab.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, mild to moderate impairment has no clinically relevant impact on olaratumab pharmacokinetics.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild (total bilirubin within normal limits and AST greater than the upper limit of normal [ULN] or total bilirubin >1 up to 1.5 times ULN and any AST) to moderate (total bilirubin >1.5 up to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, mild to moderate impairment has no clinically relevant impact on olaratumab pharmacokinetics.
Severe impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hematologic toxicity: Neutropenic fever/infection or grade 4 neutropenia lasting longer than 1 week: Withhold olaratumab until the absolute neutrophil count (ANC) is ≥1,000/mm3 and then resume with the dose permanently reduced to 12 mg/kg.
Infusion reaction:
Grade 1 or 2: Interrupt infusion; after resolution resume with the rate reduced by 50%.
Grade 3 or 4: Discontinue permanently.
Note: Doxorubicin may also require dosage modification.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Fatigue (69%), neuropathy (22%), headache (20%), anxiety (11%)
Dermatologic: Alopecia (52%)
Endocrine & metabolic: Hyperglycemia (52%), hypokalemia (21%), hypophosphatemia (21%), hypomagnesemia (16%)
Gastrointestinal: Nausea (73%), mucositis (53%), vomiting (45%), diarrhea (34%), decreased appetite (31%), abdominal pain (23%)
Hematologic & oncologic: Lymphocytopenia (77%, grades 3/4: 44%), neutropenia (65%, grades 3/4: 48%), thrombocytopenia (63%, grades 3/4: 6%), prolonged partial thromboplastin time (33%, grades 3/4: 5%)
Hepatic: Increased serum alkaline phosphatase (16%)
Neuromuscular & skeletal: Musculoskeletal pain (64%)
Ophthalmic: Xerophthalmia (11%)
Miscellaneous: Infusion related reaction (13% to 14%)
1% to 10%: Immunologic: Development of IgG antibodies (4%; all patients had neutralizing antibodies; however, therapeutic effects of antibodies could not be assessed)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to olaratumab or any component of the formulation.
Concerns related to adverse effects:
• GI toxicity: Nausea, vomiting, diarrhea, mucositis, and abdominal pain have been reported, with a higher incidence in patients treated with olaratumab and doxorubicin, compared to doxorubicin alone.
• Hematologic toxicity: A higher incidence of grade 3 and 4 lymphopenia and neutropenia have been reported in patients treated with olaratumab and doxorubicin, compared to doxorubicin alone. Thrombocytopenia (all grades) also had a higher incidence in the combination arm.
• Infusion reaction: Olaratumab is associated with infusion reactions; most infusion reactions occurred with the first or second cycle. Grade 3 or higher reactions have occurred, including a fatal case. Symptoms of infusion reactions have included flushing, dyspnea, bronchospasm, and/or fever/chills; severe cases included hypotension, anaphylactic shock, or cardiac arrest. Premedication with diphenhydramine and dexamethasone is recommended. Monitor for signs/symptoms of infusion reactions during and after infusion (resuscitation equipment should be readily available). May require treatment interruption (followed by rate reduction) or permanent discontinuation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Lartruvo: 190 mg/19 mL (19 mL [DSC]); 500 mg/50 mL (50 mL [DSC])
No
Solution (Lartruvo Intravenous)
190MG/19ML (per mL): $58.94
500 mg/50 mL (per mL): $58.94
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Lartruvo: 190 mg/19 mL ([DSC]); 500 mg/50 mL ([DSC])
Following the withdrawal of olaratumab from the global market in April 2019, patients receiving olaratumab prior to the market withdrawal may be eligible for continued access to therapy. For additional information, contact The Lilly Answers Center 1-800-LILLYRX (1-800-545-5979) or by emailing [email protected] (Note: May take up to 48 hours for a response).
IV: Infuse over 60 minutes. Do not administer as an IV push or bolus. Flush the IV line with normal saline at the end of infusion. Do not coadminister electrolytes or other medications through the same IV line.
If refrigerated, allow infusion solution to reach room temperature prior to administration. Infusion must be completed within 28 hours of dilution (when stored appropriately; see Storage/Stability).
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Olaratumab may cause teratogenicity and reproductive toxicity. Assess risk to determine appropriate containment strategy (USP-NF 2020).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Soft tissue sarcoma: Treatment (in combination with doxorubicin) of adults with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.
Note: A confirmatory phase 3 randomized, blinded trial in patients with unresectable locally advanced or metastatic STS comparing olaratumab plus doxorubicin to placebo plus doxorubicin found no significant difference in overall survival due to the addition of olaratumab to doxorubicin (Tap 2020). Due to the trial results, the manufacturer has withdrawn olaratumab from the market.
Olaratumab may be confused with obinutuzumab, ofatumumab, olaparib, omalizumab
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Females of reproductive potential should use effective contraception during therapy and for at least 3 months after the last olaratumab dose.
Based on its mechanism of action, olaratumab would be expected to cause fetal harm if administered to a pregnant woman.
It is not known if olaratumab is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 3 months following the last dose.
CBC with differential. Monitor for signs/symptoms of infusion reactions.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Olaratumab is a human (recombinant) IgG1 antibody which expressly binds to platelet-derived growth receptor alpha (PDGFR-α) to prevent binding of PDGF-AA, PDGF-BB, and PDGF-CC and block receptor activation and disrupt PDGF receptor signaling. The PDGF-alpha receptor has a role in cell differentiation, growth, and angiogenesis and has demonstrated antitumor activity in sarcomas (Tap 2016).
Distribution: Vss: 7.7 L
Half-life, elimination: ~11 days (range: 6 to 24 days)
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