COMMENTARY

When Is the Right Time to Change Practice? The Pembro Example

Mark G. Kris, MD

Disclosures

January 24, 2017

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Hello. I am Mark Kris from Memorial Sloan Kettering, speaking further about the momentous changes in the treatment of adenocarcinomas and squamous carcinomas—that is, the recent availability of data on pembrolizumab being an upfront treatment rather than chemotherapy for patients who have high-level expression of programmed death-ligand 1 (PD-L1).

Yes, this is an important development. It gives our patients new options. The results of these agents have been very good. If you have high-level expression, the adverse effects have been less than with chemotherapy, so there is every reason to recommend it for every patient.

One thing I want to talk a little bit about here is how we deal with information, and how this approval is a new world in information to the oncologist. I think the question each of us have to ask ourselves is, when would we act? When do we feel that there is sufficient information to change our way of caring for patients? I know each of us have individual standards.

In this example, I will go through the specific dates, which were very contracted. No matter what your standard, within a few days, I believe it was meant for most people.

On October 8, 2016, the data from the phase 3 randomized trial showing that pembrolizumab led to higher rates of response, progression-free survival, and overall survival for people with high-level PD-L1 expression who got pembrolizumab rather than standard cytotoxic chemotherapy [were presented at the European Society for Medical Oncology congress].[1] That happened on the 8th. On the 9th, a paper appeared in the New England Journal of Medicine describing that trial.[2]

I know many people do not change therapy on the basis of presentations at a meeting. I personally would do that, because the data have gone through a lot of review by that point. But many people wait for the publication, and it came out just 1 day later [in this case].

Obviously, there are other issues, and people want to know that there is further consideration of this results-changing therapy. It happened so quickly this time. Remember, the New England Journal of Medicine paper came out on the 9th. The National Comprehensive Cancer Network (NCCN) added upfront treatment with pembrolizumab to their guidelines on October 14th.[3]

Many people may not accept that as the ultimate standard. They will still have some concern about our reimbursement, for example. But even that [concern] was allayed on the 24th of October, when the US Food and Drug Administration (FDA) approved pembrolizumab in that situation.[4]

We went from October 8th to the 24th with the presentation at the major meeting, the New England Journal of Medicine publication, addition to the NCCN guidelines, and then FDA approval.

When to Change Practice?

I asked, when is it that you would normally change therapy? Again, I personally would change on the 8th, when we first saw this presentation at the European Society for Medical Oncology meeting in Copenhagen, but you decide. Think about when it would have been the best time to change. I advocate for the first [presentation], because the data are out there, being discussed at an international forum. A lot of time has been spent beforehand, but everybody has their own issues here. You should think about exactly what makes you change.

The other radical thought here, though, is these were not new data. In this wacky world that we have now, where clinical trial results must be reported publicly by rules of the Securities and Exchange Commission, the data were initially released on June 16th. Was that the date to act on this?

From a practical standpoint, I understand that it would be very hard for that [to happen], but the information was there. There was very sufficient information from a very careful analysis of these data, and these data did not fall from the sky.

It was very clear that these drugs were effective. They are already approved for second-line therapy. They clearly had activity in the disease that they are being used for. There was every reason to believe that they would work up front. Whether they are as good as or better than [first-line chemotherapy] is what the trial would tell us. Clearly, they work after the failure of initial treatment, and they also are tremendously less likely to cause severe side effects.

I do not know what the right answer is here. Again, practically, you may not have the ability to act on the basis of a press release, but in truth, the data were out there. I think as time goes on, we are going to find more and more contraction of the timelines between the first analysis of clinical trial data to, in this case, FDA approval.

Again, I ask you to think about where you are going to jump in here and use the data to change your care when you get really a practice-changing trial such as this. There are many different points, many different opinions, and think about what you think the right one is going to be for you and your practice.

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