Hey everyone, it’s Medicine Mondays again. I hope you liked the updated Roadmaps. I think it really helps new readers to jump into a read a bunch of posts. However, today I’m going to talk about something new today. A new drug was just recently approved by the FDA so I wanted to talk about it today. So let’s talk about “What is Keytruda?”

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What is Keytruda?

Keytruda is the trade name for Pembrolizumab. It’s an immunotherapy agent that targets the PD-1 (programmed cell death) receptor.

How does it work?

Well, I try to remind myself that the human body is actually quite remarkable. Left to its own devices most of the time, it does its best to repair itself.

Cancer is the exception.

Cancer is complex and sidesteps all of the checkpoints the body has in place to prevent it from being killed off.

The PD-1 receptor is kind of like a secret handshake the body has for itself. By expressing this receptor it is telling the body, “don’t kill me off, I’m one of the good guys”. However, in cancers that express this receptor, it makes it’s difficult for the body determine that the cell is cancerous.

Keytruda binds the PD-1 receptor on these cancer cells which prevents them from being found. Now that our own immune system can recognize that the cell is cancerous, it has no problem killing if off.

Imagine the cancerous cell is this sneaky little spy wandering around your body, slowly and silently getting stronger. He knows everyone around him and everyone knows him as “one of their own”. Keytruda basically marks him as a spy and keeps a flashlight on him, so your body can take care of him on its own.

Now, this type of immunotherapy isn’t new. However, its results are very striking.

How did it do in clinical trials?

Well, in the trials it worked remarkably well, with its results published in Science (June 8, 2017). Unfortunately, in order to read the full article, you’ll need a subscription. However, the abstract is available.

To make a long story short, the drug was administered to 86 patients, with 66 showing tumor shrinkage/stabilization and 18 who had tumors essentially resolve. These results are pretty striking.

For this reason, the Food and Drug Administration (FDA) has already approved the drug for tumors that test positive for the PD-1 receptor.

Is the PD-1 receptor mutation common?

Unfortunately, it’s not all that common. Here’s the FDA press conference link. Excerpt:

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5 percent of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells. The FDA previously approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.

(emphasis mine)

Why does this matter?

The reason this matters is for a long time scientists/physicians have been saying that classifying cancers by their location and cell type is probably not the best way.

For example, squamous cell carcinoma of the oropharyngeal cavity has different morbidity/mortality based on one small variable, whether it is HPV+ or not.

The ability to tailor treatment against the specific aberrant cell line is of huge importance. However, cancer is complex, and have multiple mutations across multiple cell lines. Treating 1 mutation, while helpful, is only part of the battle.

So, now let’s imagine the future a little bit:

A 65 y/o male goes for his yearly colonoscopy and they find a polyp. It comes back as neoplastic. Normally, the tissue would be stained and typed. It comes back as having 10 different immune markers which the patient is negative and positive for. Based on these immune markers, the patient receives a customized treatment with multiple immunotherapy drugs. He may or may not require a standard chemotherapy regiment.

I think the metaphor for this would be having a bunch of snipers on your side picking off the bad guys rather than just dropping bombs everywhere.

Will this happen in our lifetimes?

I hope so.

I’ve been hearing about immunotherapy since I started med school back in 2003. I was very optimistic and hoped that by the time I was a practicing physician that it would be very common.

However, it’s 2017, and while a lot of progress has been made in immunotherapy, it still hasn’t changed the oncology landscape all that much. I am hopeful that as we uncover more immune markers, we will gather an arsenal of immunotherapy agents. Everyone always talks about “curing cancer”. However, cancer isn’t that simple.

It’s not just: lung cancer or colon cancer / squamous cell carcinoma or adenocarcinoma / PD-1 positive or HPV positive. It’s all of those things. 

I’m optimistic that as we continue to learn more, we will be able to do more.

TL;DR

Keytruda is a new drug which targets the PD-1 receptor, with good results in specific patients.

Immunotherapy has made progress and will continue to do so.

I hope in my lifetime that we will have the ability to tailor immunotherapy for every patient individually… hopefully curative.

-Sensei

Agree? Disagree? Questions, Comments and Suggestions are welcome.

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