Nintedanib for Mesothelioma

What is Nintedanib?

The U.S. Food and Drug Administration (FDA) first approved nintedanib (Ofev) in 2014 as a treatment for progressive lung scarring. In Europe, a version of the drug named Vargatef was also approved for use in chemotherapy for lung cancer.

In 2016, the FDA granted Ofev orphan drug designation for mesothelioma in response to promising phase II clinical trial results.

This designation encourages drug development for rare diseases. Other clinical trials of Ofev for mesothelioma are ongoing.

How Does Ofev Work?

Ofev blocks tyrosine kinase, an enzyme that triggers scar-tissue growth and blood-vessel development.

Blocking tyrosine kinase also reduces tumor growth and promotes tumor-cell death in certain types of cancer.

Ofev is approved in the U.S. to treat idiopathic pulmonary fibrosis, a disease where lung scarring makes breathing progressively harder. The drug can slow down the buildup of scar tissue in the lungs.

Asbestosis is a type of pulmonary fibrosis, so Ofev is a potential treatment for asbestosis.

A 2018 Clinical Cancer Research study explains how Ofev may also be effective against malignant pleural mesothelioma.

Laboratory experiments showed Ofev inhibits mesothelioma cell growth and prevents tumors from growing blood vessels. The study results suggested Ofev may work better than bevacizumab, a similar drug being tested in mesothelioma chemotherapy.

Ofev information
Name	Ofev
Alternate Names	Nintedanib, Vargatef
Manufacturer	Boehringer Ingelheim
Dosage	200 mg twice daily
Administration Route	Oral
Active Ingredient	Nintedanib
Drug Class	Tyrosine Kinase inhibitor
Medical Code	BIBF 1120
Related Drug	Pirfenidone
Interacting Drug	Erythromycin, rifampicin, carbamazepine, phenytoin, St. John’s wort, warfarin, carbamazepine
Medical Studies	Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial
FDA Warning	Liver problems, gastrointestinal disorders, fetal toxicity, cardiovascular events, bleeding problems, gastrointestinal perforation

Ofev in Mesothelioma Clinical Trials

Ofev has reached phase III in the clinical-trial process. If it continues to show strong results in the coming years, the FDA may add it to the standard of care for mesothelioma.

In 2013, cancer centers worldwide began to test Ofev for mesothelioma as part of phase II and III clinical trials called LUME-Meso.

The trial recruited pleural mesothelioma patients with the epithelioid or biphasic cell type. The patients could not be eligible for surgery or have already received chemotherapy.

Participants in the trial were randomized into two groups. One group received standard chemotherapy plus Ofev, while the other received chemotherapy plus a placebo. LUME-Meso is a double-blind trial, meaning neither patients nor their doctors knew who received a placebo.

By 2016, the combination had proven safe, and the trial had proceeded to phase III. Its goal is to confirm that the combination is more effective than standard chemotherapy alone.

The Phase III results are not expected until late 2019, but the Phase II findings showed promise. A 2017 article in the Journal of Clinical Oncology detailed the outcomes for 87 participants.

Median survival was 20.6 months for epithelioid patients receiving Ofev, compared to 15.2 months for those receiving placebos.

Patients on Ofev were more likely to experience low white blood cell counts, but serious side effects were actually less common in the experimental group overall.

Though the LUME-Meso trial is no longer recruiting, pleural mesothelioma patients may be eligible for other clinical trials involving Ofev.

Side Effects of Ofev

The most common side effects of Ofev are gastrointestinal problems such as diarrhea, nausea and abdominal pain. Patients should alert their doctor immediately if they experience severe stomach pain, vomiting, sudden dizziness or bleeding problems.

Women who are pregnant or breastfeeding should avoid taking Ofev. The drug is also not recommended for people with liver problems.