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What’s the Truth in Oncology?
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Released: July 29, 2024

Expiration: July 28, 2025

John Marshall
John Marshall, MD

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Science of the Week: Risk Reduction vs Absolute Change
[00:05:01] What we're going to really drill down on today scientifically is a single paper. This is a breast cancer adjuvant paper published in JCO not too long ago. And the drug that was added to hormone therapy in a big, randomized trial was abemaciclib. So, Priya Rastogi was the principal investigator. The full manuscript is out there. And what this was, was the five-year survival, the five-year update of this group. So, half got traditional hormone therapy for ER/PR-positive, HER2-negative, breast cancer, quote, unquote, high-risk. Breast cancer. I'm going to come back to that. Versus the same group getting the same treatment plus two years of the CDK 4/6 inhibitor abemaciclib. 5600 patients.

Let's think about what they call high-risk over there in the breast cancer world. Well, the control arm of this patient population had a 90 percent 5-year progression free. So, I mean, it's just a huge number, right? They're all doing very, very well, even though high risk. And it was, it's node positive. It's bad features on the tumor. So, as we, it is bad cancer, but they've already figured out so much now that the many of most of those people are cured. And certainly in 5 years, it's a very high number of people who are doing well, but to try and make that even better, they added 2 years of abemaciclib. And this drug comes with diarrhea and neutropenia, sometimes severe, sometimes requiring dose modifications.

Would you take it or not? Well, let's look at the data. Well, the data, um, and the curves do show an improvement in distant relapse. Okay, of about 7 percent with a hazard ratio of 0.67, right around there, and, by any study in my world, this would be a home run. And I think it was pretty positive in the breast cancer world too, but you could think of it a couple of different ways. Remember, Already, the vast majority of these patients were cured or certainly disease free, with just the hormone therapy that they were on, and so to add on this, you know, you could say, well, you reduced the risk by a certain amount. You know, the risk was already small, 7%. You know, such a small number. So, if you treat 100 women for 2 years, you pick up a few.

But then what this paper was all about was overall survival. And I'm going to try and show you that. You see that curve? That's the bottom curve there. That's overall survival. And of course, at five years, there was no difference in overall survival. And even though this paper does, sort of engender changing the standard of care, you treat a hundred women with this situation. You give a bunch of them side effects, there's cost. And in fact, you haven't changed the overall survival. And most of them were already okay. And you did bump it a little bit.

How do you present that data to a patient? Do you use hazard ratios? Do you use treat 100 people? It only helps one. Do you present overall survival and say it's not worth it? Or do you have sort of a risk avoidance for yourself where you don't want to have been wrong. You have a patient on the other side who's afraid and will do almost anything to get out of this. Right? So, they're willing to risk toxicity, even for a very low percentage, or at least most people are. And so, it’s all aligned. The stars are aligned. to add this medicine for everyone. And so, we are really dramatically overtreating most of these people. If we were to add this drug to everyone, because most of them didn't benefit, most of them don't need it. It's only a small proportion of the patients who really get benefits. So, I think as we are presenting new science or as we are presenting options to patients, we need to be aware of this.