Olaratumab is a monoclonal antibody medication that was developed for the treatment of certain types of cancer. Specifically, it was designed to target and inhibit a protein called platelet-derived growth factor receptor alpha (PDGFR-α), which is often overexpressed in some cancer cells and plays a role in cancer growth and progression.

Olaratumab was primarily used in combination with another chemotherapy drug called doxorubicin for the treatment of advanced soft tissue sarcoma (STS) in adult patients. Soft tissue sarcomas are a group of rare cancers that originate in the soft tissues of the body, such as muscles, fat, nerves, and blood vessels. This combination therapy was approved by the U.S. Food and Drug Administration (FDA) in 2016 under accelerated approval based on early clinical trial data.

Lartruvo (Olaratumab) inhibits platelet-derived growth factor-alpha. It was used in the treatment of soft tissue sarcomas, however, because of minimal clinical advantage, the drug is being withdrawn from the market [Ref].

Lartruvo (Olaratumab) Uses:

• Soft tissue sarcoma:
  • With soft tissue sarcoma (STS) treatment (in combination with doxorubicin) of adults with a histologic subtype for which an anthracycline-containing regimen is appropriate & which is not amenable to curative treatment with radiotherapy or surgery.

Note:

• In patients, a phase III confirmatory trial with unresectable locally advanced or metastatic STS comparing olaratumab plus doxorubicin to placebo plus doxorubicin found no improvement in overall survival due to the addition of olaratumab to doxorubicin.
• The manufacturer is withdrawing olaratumab from the market due to the trial results.

Lartruvo (Olaratumab) Dose in Adults

Note:

• Olaratumab was a drug combined with another drug called doxorubicin to treat a type of cancer called soft tissue sarcoma.
• But in a big study in 2019, they found that adding olaratumab didn't really help patients live longer compared to just using doxorubicin alone.
• Because of these results, the company that makes olaratumab decided to stop selling it.

Lartruvo (Olaratumab) Dose in the treatment of Soft tissue sarcoma:

• It was given through an IV (a drip into the vein) at a specific dose on the 1st and 8th days every 3 weeks. This was mixed with another drug called doxorubicin.
• This combination was given for 8 times (we call these "cycles").
• After those 8 cycles, only olaratumab was given by itself until the cancer got worse or the side effects became too much.
• To prevent heart problems from doxorubicin, another medicine called dexrazoxane was given from the 5th to the 8th cycle.

Before starting the very first dose of olaratumab, patients were given two other medicines to prevent side effects: diphenhydramine and dexamethasone.

Lartruvo (Olaratumab) Dose in Childrens

The safety and efficacy of the drug in children have not been established

Olaratumab Pregnancy Risk Category: N (Not assigned)

• Olaratumab can harm an unborn baby if given to a pregnant woman because of how it works.
• So, women who can become pregnant should use reliable birth control methods while on this drug and continue for at least 3 months after the last dose to ensure safety.

Use of Olaratumab while breastfeeding

• We don't know if olaratumab gets into breast milk.
• But to be safe, the company that makes it advises mothers not to breastfeed while taking the drug and for 3 months after the last dose, because it might cause serious side effects for the baby.

Lartruvo Dose in Kidney Disease:

• For patients with a kidney function measurement (CrCl) between 30 to 89 mL/minute: The manufacturer doesn't suggest any changes to the usual dosage of olaratumab. Also, having mild to moderate kidney problems doesn't really affect how the drug works in the body.
• For patients with a kidney function measurement (CrCl) less than 30 mL/minute: The manufacturer doesn't give any guidance on how to adjust the dosage because they haven't studied it in people with this level of kidney problem.

Lartruvo Dose in Liver Disease:

• For mild to moderate liver problems: The manufacturer doesn't suggest changing the usual dosage of olaratumab. Also, having mild to moderate liver issues doesn't really change how the drug works in the body.
• For severe liver problems: The manufacturer doesn't give any guidance on dosage adjustments because they haven't studied the drug in people with this level of liver problem.

Common Side Effects of Olaratumab (Lartruvo):

• Central Nervous System:
  • Fatigue
  • Neuropathy
  • Headache
  • Anxiety
• Dermatologic:
  • Alopecia
• Endocrine & Metabolic:
  • Hyperglycemia
  • Hypokalemia
  • Hypophosphatemia
  • Hypomagnesemia
• Gastrointestinal:
  • Nausea
  • Mucositis
  • Vomiting
  • Diarrhea
  • Decreased Appetite
  • Abdominal Pain
• Hematologic & Oncologic:
  • Lymphocytopenia
  • Neutropenia
  • Thrombocytopenia
  • Prolonged Partial Thromboplastin Time
• Hepatic:
  • Increased Serum Alkaline Phosphatase
• Neuromuscular & Skeletal:
  • Musculoskeletal Pain
• Ophthalmic:
  • Xerophthalmia
• Miscellaneous:
  • Infusion Related Reaction

Less Common Side Effects of Olaratumab (Lartruvo):

• Immunologic:
  • Development of IgG antibodies

Contraindications to Olaratumab (Lartruvo):

In the US, the manufacturer hasn't listed any reasons a person shouldn't take olaratumab.

But in Canada, they say that if someone is allergic to olaratumab or any part of the drug, they shouldn't take it.

Warnings and precautions

Toxicity to the GI:

• Stomach and gut side effects like feeling sick, throwing up, diarrhea, mouth sores, and belly pain have been seen more often in people who took both olaratumab and doxorubicin, compared to those who took just doxorubicin by itself.

Hematologic toxicities:

• Blood-related side effects were more common in people who took both olaratumab and doxorubicin.
• Specifically, they saw more serious cases of low white blood cells (lymphopenia and neutropenia) compared to those who took just doxorubicin by itself.
• Also, a decrease in platelets, which help the blood to clot (thrombocytopenia), was more common in the group getting both drugs.

Infusion reaction

• Taking olaratumab can cause reactions while or after it's being given through an IV (infusion).
• Most of these reactions happened during the first or second time getting the drug.
• Some reactions were severe, with one even leading to death.
• People have reported symptoms like face reddening, trouble breathing, wheezing, and fever or chills.
• Really bad cases involved very low blood pressure, severe allergic shock, or the heart stopping.

• To help prevent these reactions, doctors recommend giving two medicines, diphenhydramine and dexamethasone, before the olaratumab.
• During and after the olaratumab infusion, it's essential to watch closely for any signs of these reactions.
• It's also important to have emergency equipment ready just in case.

Olaratumab: Drug Interaction

Monitoring Parameters:

Blood Tests

• CBC with differential: This is a blood test to check the different types of cells in your blood.

Infusion Reactions

• Watch for reactions when olaratumab is being given.
• Symptoms can include:
  • Face reddening
  • Trouble breathing
  • Wheezing
  • Fever or chills

If any of these symptoms appear, inform the medical team immediately.

How to administer Olaratumab (Lartruvo)?

Infusion Time:

• Give over 1 hour. Don't give it quickly (no push or bolus).

After Infusion:

• Clean (flush) the IV line with saltwater (normal saline).

What Not to Do:

• Don't give other medicines or electrolytes through the same IV line at the same time.

Temperature Before Giving:

• If it's been in the fridge, let the solution warm up to room temperature first.

Time Limits:

• After mixing the solution, you must finish giving it within 28 hours, but only if stored properly. Check storage guidelines.

Mechanism of action of Olaratumab (Lartruvo):

• Olaratumab is a type of antibody made to look like ones naturally found in our bodies.
• It's designed to stick to a protein called "platelet-derived growth receptor alpha" or PDGFR-α.
• By doing this, it stops other things, like PDGF-AA, PDGF-BB, and PDGF-CC, from attaching to PDGFR-α and turning it on.
• This helps in blocking a process called "PDGF receptor signaling," which is involved in making cells grow, develop, and form new blood vessels.
• This blocking action has been shown to be helpful in treating certain types of cancer called sarcomas.

Distribution:

• After getting into the body, olaratumab spreads out and occupies a space equivalent to about 7.7 liters, which is roughly the volume of a mid-sized fish tank.

How long it stays in the body:

• On average, it takes about 11 days for half of the drug to leave the body. But this can vary between 6 to 24 days for different people.

International Brands of Olaratumab:

• Lartruvo

Olaratumab Brand Names in Pakistan:

Not available.