From Clinical Trials to Clinical Practice: COX-2 Inhibition

This transcript has been edited for clarity. 
Hello. I’m Dr Maurie Markman, from City of Hope. I would like to briefly talk about the results of a clinical trial, but more important, the broader question of what do we do with this information as relates to the patients that we’re caring for outside of the research setting? 
The study itself was very interesting and, in my opinion, an important study that was extremely well done. This is a follow-up, and the title is “Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition In PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).” There are many words and it’s complex. This was reported in the Journal of Clinical Oncology. 
What were the results? This is my interpretation beyond what was written in the conclusion of the paper. It was extremely well done by national cooperative groups. There were almost 1200 patients in this trial who had their tumors molecularly sequenced, and they found that there were a total of 259 patients who had PIK3CA functional mutations.
These are very well described, with pathways understood. It has been hypothesized that aspirin, or COX-2 inhibitors such as celecoxib, which has obviously been available generically for a long time, might favorably impact outcomes in colon cancer. It’s potentially low risk and surely not expensive.
In this large phase 3 randomized trial, the whole population was treated with standard chemotherapy plus or minus celecoxib. In a preplanned subgroup analysis — this wasn’t something they did at the end — they looked at the particular patients with this mutation. Overall, there was no impact of adding the COX-2 inhibitor to adjuvant therapy in terms of improving overall survival in the population.
However, in that subgroup that had this functional mutation, there was a statistically significant improvement in disease-free survival, with a hazard ratio of 0.56 and, importantly, an improvement in overall survival, with a hazard ratio of 0.44, which is more than a 50% reduction of the risk for death. Again, that’s a statistical term, suggesting the potential utility of knowing whether this mutation is present.
It’s a subset of the whole population, but it’s not a small subset. It’s a meaningful subset. Again, this suggests the potential utility of using this relatively well-tolerated, inexpensive medication as an adjuvant in standard practice in patients with colon cancer. 
The question to be asked is, when would something like this truly become standard of care? This does not mean that you have to give it to every patient nor that you have to do this testing on every patient. But it does mean that you should discuss it with the patient and make it available, perhaps asking a patient if they would like to get this test done, and if it’s positive, would they be interested in potentially receiving this medication, because we now have data. (These weren’t the only data available either.)
This is a nice trial and a nice paper; the investigators should be applauded. It’s all very interesting, but that does not impact the next patient being seen in an oncologist’s office with colon cancer. What impacts the patient is discussing the results of this and other well-designed trials, talking about the implications of the testing and the treatment, and whether they, after appropriate discussion and review of the research themselves, want to potentially be using that treatment.
The bottom line is that we cannot simply leave this as words on a piece of paper, in an internet publication, or on social media, but actually apply it to the patient. How do we move that? How do we make the decisions? How do we make it available? How does it potentially become standard of care? 
There are many questions, and I suggest that we need to come up with answers. Thank you for your attention.