How does the cancer drug Keytruda work? And how is it different to chemo?

Nial Wheate, Macquarie University

From today, the Australian government will expand Pharmaceutical Benefit Scheme (PBS) access to the drug Keytruda for three additional types of cancer.

This is part of a broader shift away from cancer treatment with traditional chemotherapy drugs that can be less effective and have more intense side effects.

So what is Keytruda? How does it work? And which cancers can it treat?

The problems with standard chemo

Most chemotherapy drugs developed in the 1950s to 1990s are small molecules that scientists refer to as cytotoxics. This means they mess with the internal processes of cancer cells so much that the cancers essentially shut themselves down.

But cytotoxics can’t tell the difference between cancerous and healthy cells. So they attack all fast-growing cells. Cancers are comprised of fast-growing cells, but so is the lining of the gastrointestinal tract, bone marrow and hair.

Damage to these healthy cells leads to the typical chemotherapy side effects many patients experience. Damage to the stomach and intestines causes nausea, vomiting and diarrhoea.

Bone marrow damage leads to lethargy because of low red blood cell numbers. Low levels of white blood cells increase susceptibility to infection.

Hair loss occurs not just on the head and body but also in the ears, which can cause hearing loss.

The intensity of the side effects limits the amount of cytotoxic drugs that can be given to a patient. This in turn limits how successful that drug is in treating the cancer.

How Keytruda is different

Unlike the small-molecule cytotoxics, Keytruda (pembrolizumab) is a large protein-based drug from a family of medicines called monoclonal antibodies.

Monoclonal antibodies are highly selective for cancer cells, and harm healthy cells much less than cytotoxics. Their side effects therefore tend to be milder, although doctors still need to manage them.

To understand how Ketruda works, we need to know about the protein PD-1. This is a protein the body uses as an immune system brake to stop itself attacking healthy cells.

But some cancers express a protein on their surface called PD-L1, which stops immune system T-cells with PD-1 from attacking the cancer.

PD-1-targeting drugs, including Keytruda, work by blocking PD-L1’s interaction with PD-1. This turns the immune system back on so the body can fight the cancer itself.

Keytruda was the first in its class to do this.

How long has it been around?

Keytruda was first approved in 2014 to treat advanced melanoma.

It’s had a major impact on melanoma treatment and the five-year overall survival rate: how many patients live for five or more years after diagnosis.

Since in the introduction of Keytruda, the five-year survival rate for advanced melanomas has increased from less than 10% to more than 55%.

It’s now used to treat other types of cancer

Keytruda has become an essential medicine to treat many other types of cancer.

Oncologists have been prescribing Keytruda on the PBS for cervical cancer, a type of kidney cancer called renal cell carcinoma, a type of breast cancer called triple negative breast cancer, and squamous cell carcinoma cancers of the pharynx, larynx and mouth.

The new PBS listings for Keytruda are for advanced bile duct (cholangiocarcinoma) and ovarian cancers, and a rare form of skin cancer called Merkel cell carcinoma.

Bile duct cancers are a rare but deadly form of cancer that affect around 1,400 people per year. Without Keytruda, the five-year survival rate is around 5%. A recent study found after the introduction of Keytruda, survival increased to more than 16%.

If caught early, ovarian cancer has a five-year survival rate of 70–95%, but this drops to 10–40% for advanced ovarian cancers. While a five-year survival rate has not been established, recent research has shown treatment with Keytruda can increase the 18-month survival rate for advanced ovarian cancer from 40% to 50%.

For Merkel cell carcinomas, treatment with Keytruda increases five-year survival for advanced forms of this cancer from 34% without the drug to 43% with the drug.

How much does Keytruda cost patients?

The cost of cancer treatment in Australia, including drugs like Keytruda, is mostly free, as part of a public patient’s hospital treatment. But there can be some out-of-pocket costs and, if charged for the drug, the PBS price is just A$25 for general patients and $7.70 concession.

In contrast, private patients may pay up to $14,800 per non-PBS script for Keytruda.

A PBS listing for these new types of cancers will save ordinary Australians significant money at a time when their finances will already be impacted by the disease.

This article is republished from The Conversation under a Creative Commons license. Read the original article.