drug-monograph

olaratumab

Other Names

Lartruvo

Appearance

solution

mixed into larger bags of fluids

A - Drug Name

olaratumab

COMMON TRADE NAME(S): Lartruvo(TM) ()

B - Mechanism of Action and Pharmacokinetics

Olaratumab is a targeted recombinant human immunoglobulin (IgG1) that binds to PDGFR-alpha, inhibiting its signaling pathway in tumour and stromal cells.

Distribution

Olaratumab exhibits nonlinear pharmacokinetics with steady state concentrations reached during cycle 3 in the phase IIb/II study (Davis 2017).

Metabolism

Monoclonal antibodies are degraded into small peptides and amino acids via catabolic pathways.

Elimination

Half-life

(elimination) is approx.11 days

C - Indications and Status

Health Canada Conditional Approvals
(pending the result of studies to verify the drug’s clinical benefit. Patients should be advised of the nature of the marketing authorization granted.)

In combination with doxorubicin for the treatment of patients with advanced soft tissue sarcoma (STS) not amenable to curative treatment with radiotherapy or surgery and for whom treatment with anthracyclines is appropriate.

Note: Conditional approval was based on an overall survival benefit found in a randomised phase II study. Clinical benefit needs validation from a phase III trial.

**Important - New Information as of January 2019**:

Results of a phase 3 RCT trial did not confirm the clinical benefit of olaratumab in combination with doxorubicin as compared to doxorubicin alone. Based on the information available so far, no new safety concerns were identified during the study. Patients who currently are receiving olaratumab should discuss with their physician whether to continue their course of therapy. Olaratumab should not be initiated in new patients outside of an investigational setting.

D - Adverse Effects

Emetogenic Potential:

Low

Extravasation Potential: None

The following adverse effects include those reported in the phase II STS study where the difference between olaratumab and doxorubicin compared to doxorubicin alone was ≥ 5%.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Dermatological	Alopecia (52%)	E D
Gastrointestinal	Abdominal pain (23%)	E
	Anorexia, weight loss (31%)	E
	Diarrhea (34%)	E
	Mucositis (53%)	E
	Nausea, vomiting (73%)	E
Hematological	INR / prothrombin time increased (33%) (aPTT increased)	E
	Myelosuppression ± infection, bleeding (55%) (grade 3, 4)	E
Hypersensitivity	Infusion related reaction (13%) (3% severe)	I E
Metabolic / Endocrine	Abnormal electrolyte(s) (21%) (8% severe hypokalemia)	E
	Hyperglycemia (52%)	E
Musculoskeletal	Musculoskeletal pain (64%)	E
Nervous System	Anxiety (11%)	E
	Headache (20%)	E
	Neuropathy (22%)	E
Ophthalmic	Dry eye (11%)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for olaratumab include nausea, vomiting, musculoskeletal pain, myelosuppression ± infection, bleeding, mucositis, alopecia, hyperglycemia and diarrhea.

The majority of infusion-related reactions, including severe and fatal reactions occurred during or following the first infusion and may occur despite the use of premedication. Risk of anaphylaxis is associated with elevated IgE levels against galactose-alpha-1-3-galactose. Monitor patients closely during and after infusions. See the Dosage with Toxicity section for management recommendations.

Increased rates of severe neutropenia have been reported in patients receiving olaratumab in combination with chemotherapy compared to those receiving chemotherapy alone.

In clinical trials, neutralizing antibodies against olaratumab were detected in 3.5% of evaluable patients. Effects on efficacy, safety and exposure could not be assessed.

E - Dosing

Refer to protocol by which patient is being treated.

For cycle 1, premedicate all patients with an H1 antihistamine (e.g. diphenhydramine) and dexamethasone (or equivalent) intravenously 30-60 minutes prior to infusions. For subsequent cycles, premedicate all patients with an H1 antihistamine 30-60 minutes prior to infusions (unless prior infusion reaction - see dosage with toxicity table below).

Adults:

Cycles 1 to 8*:

olaratumab 15 mg/kg IV days 1 and 8 with

doxorubicin 75 mg/m²IV day 1 every 21 days

*doxorubicin is given for up to 8 cycles. Note that in the clinical trial, all patients received dexrazoxane to minimize cardiac toxicity.

Subsequent cycles:

olaratumab 15 mg/kg IV days 1 and 8 every 21 days until disease progression or unacceptable toxicity

Dosage with Toxicity:

In the phase II study, if doxorubicin was discontinued due to toxicity, olaratumab monotherapy was continued. Similarly, if olaratumab was discontinued due to toxicity, doxorubicin was continued for up to 8 cycles in the absence of related toxicity. Reduced doses were not re-escalated.

Dose level	Olaratumab dose
0	15 mg/kg
-1	12 mg/kg
-2	10 mg/kg
-3	Discontinue

The following are suggested dose modifications for olaratumab. For doxorubicin dose modifications, please refer to the doxorubicin drug monograph.

Toxicity	Severity	Olaratumab dose
Infusion related reactions	Grade 1 or 2	Hold and administer acetaminophen, H1 antihistamine and dexamethasone (or equivalent) as needed. Upon recovery, restart at 50% reduced infusion rate. For subsequent infusions, premedicate with acetaminophen, H1 antihistamine and dexamethasone (or equivalent) and maintain reduced infusion rate.
	Grade 3 or 4	Permanently discontinue.
Neutropenia	Grade 4 for > 7 days or Febrile neutropenia	Hold until ANC ≥ 1 x 10⁹/L, then reduce 1 dose level.
Other	1st occurrence Grade 3 or 4 not manageable with supportive care	Hold until toxicity ≤ grade 1 or baseline. Reduce 1 dose level.
	Recurrent grade 3 following 1 dose level reduction	Reduce 1 dose level.
	Recurrent grade 4 following 1 dose level reduction	Permanently discontinue.

Dosage with Hepatic Impairment:

No formal studies have been done; patients with grade 2 or higher LFT abnormalities were excluded from the clinical trial.

Hepatic impairment	Olaratumab dose
Mild (AST > ULN or total bilirubin > 1-1.5 x ULN)	no change
Moderate (total bilirubin > 1.5-3 x ULN)	no change
Severe (total bilirubin > 3 x ULN and any AST)	no data

Dosage with Renal Impairment:

No formal studies have been done; patients with grade 2 or higher creatinine levels were excluded from the clinical trial.

Renal function (CrCl)	Olaratumab dose
≥ 60 ml/min	no change
30-59 ml/min	no change
< 30 ml/min	no data

Dosage in the elderly:

Clinical studies had insufficient numbers of patients aged 65 and older to determine whether they responded differently from younger patients.

Children:

Olaratumab is not indicated for pediatric use.

F - Administration Guidelines

DO NOT administer as an IV push or bolus
Dilute the drug with 0.9% saline solution to a final volume of 250 ml. Do not use dextrose as a diluent.
Mix by gentle inversion.
Infuse over 60 minutes through a separate infusion line. Flush the line with saline after administration.

Vials should be stored at 2-8^oC and protected from light.
Diluted solutions demonstrate chemical and physical stability for up to 24 hours refrigerated and up to an additional 12 hours at room temperature.
DO NOT freeze or shake vials or diluted solutions.

G - Special Precautions

Contraindications:

Patients who have a hypersensitivity to this drug or any of its components

Other Warnings/Precautions:

Severe and life-threatening infusion reactions have occurred during first administration; resuscitaion equipment should be readily available.
This treatment has been associated with fatigue; patients should exercise caution while driving or operating machinery.
Olaratumab contains 57 mg of sodium per 50 ml vial. Consider this for patients on a controlled sodium diet.

Other Drug Properties:

Carcinogenicity: Unknown

Pregnancy and Lactation:

Fetotoxicity: Likely

Olaratumab may cause fetal harm and is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 3 months after the last dose.
Excretion into breast milk: Unknown

Breastfeeding is not recommended during treatment and for at least 3 months following the last dose.
Fertility effects: Unknown

H - Interactions

No drug interaction studies have been conducted.

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline and before each cycle
Liver function tests	Baseline and before each cycle
Cardiac function tests (Echo, RNA and/or MUGA scans) for all patients with cardiac risk factors	Baseline and as clinically indicated during doxorubicin treatment
Clinical toxicity assessment for infusion related reactions, infection, bleeding, GI, skin and cardiac toxicity	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

K - References

Olaratumab (Lartruvo^TM) product monograph. Eli Lilly Canada Inc. Nov 23, 2017.

Davis EJ, Chugh R. Spotlight on olaratumab in the treatment of soft-tissue sarcoma: design, development, and place in therapy. Drug Des Devel Ther. 2017 Dec 13;11:3579-3587.

LARTRUVO (olaratumab) - New clinical trial information important to prescribing decisions. Health Canada, January 29, 2019.[Accessed February 1st, 2019]. Available from: http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/68974a-eng.php

February 2019 Updated with information from Health Canada alert

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

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Last Updated: July 21, 2026

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