FDA Approves (Opdivo and Yervoy) for Treating Mesothelioma

The US food and drug administration has recently approved a combination therapy (Opdivo and Yervoy) for the treatment of adults with unresectable malignant pleural mesothelioma. This is the first combo drug approval for mesothelioma in 16 years.

Mesothelioma is a rare and aggressive type of cancer that is caused by inhaling asbestos.

Opdivo (nivolumab)

Opdivo (nivolumab) alone is used to treat a specific type of cancers. It works with your immune system to stop the growth of cancer cells.

It may also be used in combination with other medicines to treat and prevent certain types of cancer that have already spread or can’t be removed through surgery. It is used in combination with other medications to treat many different kinds of cancers such as skin cancer, advanced lung cancer, renal cell carcinoma, head and neck cancers, blood cancers.

The most common side effects associated with the use of this medicine include fatigue, skin rash, itchy skin, weakness, cough, pain in muscles, bones, and joints vomiting, shortness of breath, diarrhoea, nausea, constipation, decreased appetite, back pain, upper respiratory tract infection.

A severe side effect of Opdivo is the immune-mediated reactions that can target your end organs. This can be serious and life-threatening. Always consult your doctor.

The usual recommended dose of Opdivo in metastatic melanoma is 240 mg in a slow IV infusion over 30 minutes every two weeks until the disease progression. It is given as a single and slow intravenous dose.

How does Opdivo and Yervoy work?

Before going into the mechanism of action let me first clear a few things;

What is PD-L1: It is a protein that works as a natural “brake” in your body, keeping the body’s immune responses in check. PD-L1 can be found in higher than average amounts in some normal cells and some types of cancer cells. When PD-L1 binds to another protein called PD-1 (a protein found on T cells), it prevents the T cells from killing cells that contain PD-L1, including cancer cells. Cancer drugs, so-called immune checkpoint inhibitors, bind to PD-L1 and block its binding to PD-1. This releases the “brakes” on the immune system and releases the T cells to kill cancer cells.

Opdivo (nivolumab) is a human immunoglobulin G4 (IgG4) monoclonal antibody. It binds to the PD-1 receptor and inhibits/blocks its interaction with PD-L1 and PD-L2, thereby inhibiting the PD-1 pathway-mediated inhibition of the Immune response is cancelled. , including the anti-tumour immune response. The binding of the PD-1, PD-L1 and PD-L2 ligands to the PD-1 receptor found on T cells inhibits T cell proliferation and cytokine production. PD-1 ligands are upregulated in some tumors, and signal transmission through this pathway may help deter active T cell immune surveillance of tumors.

Yervoy (Ipilimumab)

Yervoy (Ipilimumab) is another prescription-only medicine that is used in the treatment of a different type of cancers such as melanoma. It is also used in combination with other drugs such as Nivolumab to treat metastatic non-small cell lung cancer whose tumors express PD-L1, with no EGFR or ALK genomic tumor abnormalities.

Fatigue, diarrhea, itching, nausea, vomiting, and skin rashes are some of the widespread side effects affecting 30% of patients taking this medicine.

Other less common side effects (10-29%) include decreased appetite, constipation, cough, headache, abdominal pain, shortness of breath, anemia, and fever.

A very rare but more serious side effect includes an immune-mediated reaction.

How does Opdivo and Yervoy work?

It is a recombinant human monoclonal antibody that inhibits the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4).

CTLA-4 is a T cell molecule that inhibits the immune response. CTLA-4 is a negative regulator of T cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands. Blockade of CTLA-4 has been shown to increase activation and proliferation of T cells. The mechanism of action of the action of ipilimumab in melanoma patients is indirect, possibly through T-cell-mediated anti-tumor immune responses.

 

Is Yervoy a chemotherapy?

No, it fights cancer cells differently. It helps your immune system launch a response against cancer that’s greater than when either medication is used alone.

FDA Approvals of Opdivo and Yervoy

Recently The US food and drug administration (FDA) has approved these two drug combinations for the treatment of a sporadic type of cancer that is also known as mesothelioma.

Opdivo and Yervoy are already approved for the first-line treatment for metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1.

It is also used in combination with limited chemotherapy for the first-line treatment of adults with metastatic or recurrent NSCLC with no EGFR or ALK mutations regardless of PD-L1 expression.

It is the first new combo drug approved for mesothelioma in 16 years and only the second systemic therapy in history.

The historic approval of a treatment for this cancer without a cure was the first since the FDA approved the chemotherapy combination of pemetrexed and cisplatin in 2004.

The drug company Bristol Myers Squibb, which makes Opdivo and Yervoy, respectively, was approved on October 2.

The approval follows a multicentre international clinical phase III study in which the combination demonstrated superior overall survival compared to chemotherapy alone. The name of the survey sponsored by Bristol Myers Squibb was CheckMate 743.

Patients treated with the immunotherapy combination Opdivo and Yervoy had a median overall survival of 18.1 months compared with 14.1 months for patients who received chemotherapy alone.

The 2-year survival rate was 41% for those who received the combined immunotherapy, but only 27% for the chemotherapy group.

Although the overall improvement in survival was modest, it was dramatic for the traditionally difficult-to-treat subtypes of mesothelioma.

In patients with sarcomatoid or biphasic mesothelioma (non-epithelioid histology), the median survival was only 8.8 months for those who received chemotherapy. For those who received immunotherapy, it was 18.1 months.

The two-year survival rate increased from 8% to 38% for the same two categories. The results were presented at the virtual meeting of the World Conference on Lung Cancer earlier this year.

After the promising data from the Phase 3 CheckMate-743 trial (NCT02899299), The European Medicines Agency also agreed to examine Bristol Myers Squibb’s application for approval of the combo immunotherapy regimen Opdivo (nivolumab) and Yervoy (ipilimumab) for untreated inoperable malignant pleural mesothelioma (MPM).


This article is written and reviewed by Manzoor Pharm.D (Doctor Of Pharmacy) 

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