Cancer Journal – The Combined Positive Score

I have a bit of good news concerning my Combined Positive Score (CPS, although I have also seen Composite Proportion Score). The CPS is a biomarker that helps predict whether my current treatment regimen, immunotherapy, will succeed. This post will explain what the CPS is and why it matters.


Let’s review what immunotherapy is and how it works. Cancer is the uncontrolled growth of the body’s cells. The control has to break in at least two ways. First, something damages the machinery in a cell that regulates the cell’s reproduction. Second, the tumour also needs to escape the body’s immune system.

In the immune system, T-cells search for and destroy cancer cells. This is great, but if the T-cells get too aggressive and start attacking normal body tissues, we have an autoimmune disease. To prevent this, the body has evolved mechanisms that can suppress the T-cells.

The PD-1/PD-L1 pathway is one of these mechanisms. PD-1 is a receptor protein on the T-cell’s surface. It triggers programmed cell death; in effect, it’s an off-switch on the T-cell. If another cell can bind to this receptor using a protein called PD-L1, the T-cell kills itself.

Unfortunately, this pathway allows the tumour to evade the immune system. If the tumour gets a mutation that allows it to express a lot of PD-L1, it can suppress the T-cells. Then the tumour can continue its uncontrolled reproduction.
Here is where the immunotherapy drugs come in. I am taking pembrolizumab, a molecule that interrupts the PD-1/PD-L1 pathway. With the pathway broken, the T-cells can attack and shrink the tumour.

Sounds good, but unfortunately, the drug doesn’t work very often. In the first trial of pembrolizumab with recurrent head and neck cancer — like me — only 18% of patients responded to the drug. However, some of the responders had several years of remission (the period during which cancer stopped progressing). Averaged over all patients, the drug resulted in only 1.5 extra months of life. However, the better way to describe the results is that most patients didn’t benefit, but a few patients benefited a lot.

The Combined Positive Score

So why did the drug work in a few patients but not others? I’m not sure anyone really knows the answer. Still, there is some evidence that patients with high CPS values are more likely to be responders. The CPS estimates the proportion of tumour cells that express PD-L1, one of the molecules in the PD-1/PD-L1 pathway. The idea that tumours expressing a lot of PD-L1 would be most vulnerable to pembrolizumab makes sense. In any event, patients with CPS ≥ 20 were the best responders. And — drumroll, please! — on 2021-06-23, I learned that my CPS = 21!

This doesn’t mean that it’s certain that pembrolizumab will work for me. It’s a biomarker that may predict successful treatment; it’s not a measure of treatment success. It’s based on a limited amount of data. Many biomarkers that look promising in early studies fade as evidence accumulates. And even in those studies, some of those with high CPS values did poorly. If you have followed the Cancer Journal, you may recall that my tumour is p16+, a biomarker with lots of data that strongly predicts treatment success. And yet, my radiotherapy failed.

Where I’m At

So, I’m still facing daunting odds. But this is the first good news in months, and it strengthens my hope. It helps my resolution to eat well and maintain my workout discipline. Immunotherapy is unlikely to cure me. But I might have time to visit Tuscany again with my wife. And, perhaps, to finish my book.

  • If you know someone with cancer, consider sending them a link to this post.
  • To read the Cancer Journal from the start, please begin here.
  • The next post is here.
  • A table of contents for the Cancer Journal is here.
  • To get the Cancer Journal in email, go here.


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