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Lartruvo

Generic Name: Olaratumab
Class: Antineoplastic Agents

Introduction

Olaratumab is an antineoplastic agent.

Uses for Lartruvo

Olaratumab has the following uses:

Olaratumab is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody indicated, in combination with doxorubicin, for the treatment of adult patients 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.1

This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.1

Lartruvo Dosage and Administration

General

Olaratumab is available in the following dosage form(s) and strength(s):

Injection: 500 mg/50 mL (10 mg/mL) solution in a single-dose vial.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • Administer olaratumab at 15 mg/kg as an intravenous infusion over 60 minutes on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.1

  • For the first 8 cycles, olaratumab is administered with doxorubicin.1

  • Premedicate with diphenhydramine and dexamethasone intravenously, prior to olaratumab on Day 1 of cycle 1.1

  • For intravenous infusion only. Do not administer as an intravenous push or bolus.1

Cautions for Lartruvo

Contraindications

None.1

Warnings/Precautions

Infusion-related Reactions

Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of olaratumab across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. 1

Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed olaratumab; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N = 485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. 1

Monitor patients during and following olaratumab infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue olaratumab for Grade 3 or 4 IRR. 1

Embryo-fetal Toxicity

Based on animal data and its mechanism of action, olaratumab can cause fetal harm when administered to a pregnant woman. Animal knockout models link disruption of PDGFR-α signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis caused malformations and skeletal variations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with olaratumab and for 3 months after the last dose. 1

Specific Populations

Pregnancy

Based on animal data and its mechanism of action, olaratumab can cause fetal harm. There are no available data on olaratumab use in pregnant women. No animal studies using olaratumab have been conducted to evaluate its effect on female reproduction and embryo-fetal development. Animal knockout models link disruption of PDGFR-α signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis at exposures less than the exposure at the maximum recommended human dose caused malformations and skeletal variations.1 In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. 1

No animal studies have been conducted using olaratumab to evaluate the effect of blocking PDGFR-α signaling on reproduction and embryo-fetal development. In PDGFR-α knockout mice, disruption of PDGFR-α signaling resulted in embryo-fetal lethality and teratogenicity, including cleft face and spina bifida. Intravenous administration of an anti-murine PDGFR-α antibody once every 3 days to pregnant mice during organogenesis at 50 and 150 mg/kg resulted in increased malformations (abnormal eyelid development) and skeletal variations (additional ossification sites in the frontal/parietal skull). Increased post-implantation loss occurred at a dose of 5 mg/kg. The effects on fetal development in mice administered this antibody occurred at exposures less than the AUC exposure at the maximum recommended human dose of 15 mg/kg olaratumab. 1

Lactation

There are no data on the presence of olaratumab in human milk, or its effects on the breastfed infant or on milk production. Because of the potential risk for serious adverse reactions in breastfeeding infants from olaratumab, advise women not to breastfeed during treatment with olaratumab and for 3 months following the last dose. 1

Females and Males of Reproductive Potential

Based on its mechanism of action, olaratumab can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with olaratumab and for 3 months after the last dose. 1

Based on animal models, olaratumab may impair male fertility. 1

Pediatric Use

The safety and effectiveness of olaratumab in pediatric patients have not been established. 1

Geriatric Use

Clinical studies of olaratumab did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. 1

Common Adverse Effects

The most common (≥20%) adverse reactions of olaratumab plus doxorubicin are nausea, fatigue, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache.1

The most common (≥20%) laboratory abnormalities were lymphopenia, neutropenia, thrombocytopenia, hyperglycemia, elevated aPTT, hypokalemia, and hypophosphatemia.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Olaratumab is a human IgG1 antibody that binds PDGFR-α. PDGFR-α is a receptor tyrosine kinase expressed on cells of mesenchymal origin. Signaling through this receptor plays a role in cell growth, chemotaxis, and mesenchymal stem cell differentiation. The receptor 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-α 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-α pathway signaling. Olaratumab exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models. 1

Advice to Patients

Infusion-Related Reactions

Advise patients to report signs and symptoms of infusion reactions. 1

Embryo-Fetal Toxicity

Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential of the potential risk to the fetus, to use effective contraception during treatment with olaratumab and for 3 months after the last dose, and to inform their healthcare provider of a known or suspected pregnancy. 1

Lactation

Advise patients not to breastfeed during treatment with olaratumab and for 3 months after the last dose. 1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

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.

Olaratumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Solution

10 mg/1 mL

Lartruvo

Eli Lilly and Company

AHFS Drug Information. © Copyright 2016, Selected Revisions November 7, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Eli Lilly and Company. LARTRUVO (olaratumab) INTRAVENOUS prescribing information. 2016 Oct.

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