COMMENTARY

Is Aspirin the New (Old) Immunotherapy?

David J. Kerr, CBE, MD, DSc, FRCP, FMedSci

Disclosures

March 01, 2018

Hello. I'm David Kerr, professor of cancer medicine from the University of Oxford.

For those of you who follow me on Medscape and WebMD, you know that I don't like aspirin: I love it. I think it's a wonderful drug. There's a lot of work going on just now looking at its molecular pharmacology.

There's a great recent paper published by Dr Tsuyoshi Hamada and colleagues[1] looking at the role of aspirin as an immune checkpoint blockade inhibitor. It's a lovely study. Using part of a retrospective sample collection, they were able to look at the impact of post-primary treatment use of aspirin in patients with resectable colorectal cancer.

They hypothesized that patients who had tumors with low expression of programmed cell death ligand 1 (PD-L1) would be more sensitive to the beneficial effects of aspirin. They looked at just over 600 patients. [The study used] a beautiful statistical analysis that stratified [findings] and accounted for all of the other contributory factors that might be tied up with aspirin's use: PIK3CA mutations, [CDX2 expression], and even tumor-infiltrating lymphocytes. It's what you would expect from a research group of this quality. The analysis was done very carefully indeed.

At the end of the study, they showed that their hypothesis was correct. Patients with tumors with relatively low expression of PD-L1 (also known as CB274) did better than those patients who had tumors that expressed high levels of PD-L1, for which aspirin seemed to have no benefits at all.

This all fits in with the link-up between the prostaglandin E2 pathway and immune suppression. It suggests that aspirin may be yet another potential partner drug that may enhance the activity of the huge excitement around the drugs which block the PD-L1, PD-1, the whole immune checkpoint pathway just now.

It was a really nice, very carefully conducted study. The results were quite compelling in terms of the survival benefits accrued to postsurgical use of aspirin in patients with low levels of PD-L1 expression. It again shows the importance of the microenvironment in determining the outcome of tumor behavior. This gives some potential therapeutic insight into why aspirin might be a very useful companion drug to give in combination with these rather more expensive, more complex immune blockade inhibitors.

Aspirin wins again. There's yet more plausible biological mechanism supporting its use.

I'm grateful for any comments that you may care to post. I'd be very interested in your own thoughts in the matter.

For the time being, Medscapers, over and out. Thank you.

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