A recent NZ Herald story about a young woman with recurrent nasopharyngeal cancer aroused our interest in the immunotherapy drugs Keytruda and Opdivo, approved in NZ but not funded for HNC.
Eve McGauley was only 15 when she contracted the disease. She went through the awful treatments, was in remission and then the cancer struck again. Her family decided to try Keytruda which worked well for her. Her tumours have disappeared and she feels well for the first time in ages. This is not a cure, says her friend on her Givealittle page, but it is giving Eve more quality time. It is not yet known how long the Keytruda effect works.
Keytruda and Opdvio are the advance guard of a promising but not yet curative treatment for head and neck cancer: immunotherapy drugs. They are also called checkpoint inhibitors. They inhibit the ruses cancer cells use to deceive the immune system into ignoring them. So far they seem to work only for some people and the median improvement in survival overall is measured in months not years. They are approved by the FDA only for use in advanced cases (metastatic or recurrent cancer) so are not used in front-line care yet.
The future looks as if it will be in combinations of these drugs, maybe with chemotherapy. But it's so exciting to see Keytruda work for a New Zealander. It's unfortunate that her family has had to pay for it up till now.
Because her GAL account has raised over $60,000, she now qualifies for free provision of the drug by the manufacturer, Merck.
I'm a bit confused about these treatments in spite of the many articles coming out about them so I posed myself a series of questions to find answers to
1. What are checkpoint inhibitors?
Quite simply they are immunotherapy drugs that turn off those checkpoints in the immune system that stop T-cells from attacking cancer cells.
2. What do these drugs do?
The immune system (using the killer T-cells) should kill cancer cells but these cells are smart and can use the "PD-1" pathway to hide from T-cells. When the T-cell approaches the cancer cell, the latter cell has a protein called PD-L1 which interacts with the PD-1 protein on the T-cell and tells it there's nothing wrong with it and it doesn't need to be destroyed. (See picture above: Keytuda is the antibody.)
This is where Keytruda and Opdivo and other similar drugs can step in and turn off that signal.
3. Can you test someone's cancer to see if it will respond?
Some cancer cells have large amounts of PD-L1 which helps them hide better from T-cells. Presumably these "biomarkers" will lead to a better response to checkpoint inhibitors. No biomarker is perfect, say scientists, but testing for expression of PD-L1 is potentially helpful. (PD = programmed cell death)
4. What are the side effects?
Yes, there are side effects, even in these seemingly "clean" drugs. Taking the brakes off the immune system can cause it to attack other, healthy parts of the body as with an auto-immune disease. Interestingly, Eve has reported no side effect apart from tiredness.
5. What is the difference between Opdivo and Keytruda?
From what I can tell they are very similar but are administered differently. Keytruda is made by Merck and Opdivo by Bristol Myers. Someone said they are like Coke and Pepsi.
6. What other cancers are they used for?
Pharmac funded Keytruda for melanoma patients last year. It is also used for some other cancers. See links below.
7. When will one of these drugs be funded in NZ for HNC?
Not sure. At the moment Keytruda is available in private clinics all over New Zealand. These are not miracle drugs for most people and do not have a huge survival advantage over traditional treatment. About 5% of patients in the latest big trial achieved a complete response to Keytruda (all tumours gone). Pharmac will no doubt proceed with caution as it usually does.
As research and trials continue, these drugs might be used in front-line treatment but at the moment they give a sliver of hope to people with advanced disease. The first bit of hope in a very long time.
Below are the scientific names for the two drugs plus a defintion of each from Wikipedia, lightly edited for brevity.
Pembrolizumab (trade name Keytruda) is a humanized antibody used in cancer immunotherapy. It blocks a protective mechanism on cancer cells, and allows the immune system to destroy those cancer cells. It targets the programmed cell death 1 (PD-1) receptor.
Nivolumab (Opdivo) works as a checkpoint inhibitor, blocking a signal that would have prevented activated T cells from attacking the cancer, thus allowing the immune system to clear the cancer. It was brought to market by Bristol-Myers Squibb.