Oncology Unscripted With John Marshall: Episode 9: Are You Overdosing Your Patients?

Monopoly Concerns with Oncology Acquisitions: Should We Be Worried 

[00:00:05] John Marshall, MD: John Marshall, MD: Hey, everybody, John Marshall with Oncology Unscripted, even though I've got a little bit of a script right here, but don't tell anybody. Today, we're going to talk all about dosing of medicine, and do we have it right or not, particularly with some of our newer cancer medicines. And I'm going to really drill down on a couple that I know a lot about that I hope you will use in your own practice, quite honestly, and make your life a little easier, and, more importantly, your patient's life a little easier. 

[00:00:34] Let's look a little bit at the business side of what's going on. You know, I've been kind of watching this big takeover of McKesson and Florida Cancer Specialists. Well, wouldn't you know what? There's in fact, of course, been some Federal Trade Commission pushback that this creates sort of, how could it not be a monopoly, when you've got everything from insurance to providers to drug people and everybody in the same game. It ends up becoming a monopoly out there. And, you know, I think it's right that we look at this because, you know, we do predict that there's going to be just, you know, just a few huge health care systems out there in our country. And we need to figure out how best to manage all of that to continue to provide the best care we can, for all of our patients and give access to everybody that we can get access to. So. Important stuff going on out there still, of course, in our business world. 

Science Snapshot [00:01:34] 

From a science perspective, I just came across, really yesterday, in the New England Journal, an article that that piqued my interest. Because it only went very nicely with the theme of our episode today, but around dosing, but really value in terms of what's it worth to get a little bit more survival. 

And this was a study as a metastatic lung cancer study in the New England Journal of Medicine. I've got an actual copy of it. Right there. There it is. And this is by Cho et al. It's a very important study. It's the MARIPOSA study. You all know about it. It's amivantamab, there you go, plus lazertinib, which is, I guess, like Lazarus from the New Testament, maybe, maybe not. But this is in patients with EGFR-mutated non-small cell lung cancer, and, of course, the current standard of care is osimertinib. A relatively easy medicine to take has some side effects. The doublet wins in the end of the day, by a small amount, and that's with both PFS and trending towards OS. But I went to the toxicity table because do we have the doses of these medicines correct? And so maybe that's reflected in tox, and I'll come back to this in a little bit, but you know, there's not equal toxicity at all. In fact, the doublet therapy has essentially double the amount of grade three toxicity, and the investigators are fairly bold in saying, however, the incidents of grade four, which is almost dead, and five, dead, or discontinued treatment, were similar between the two groups. So now we've elevated it. Don't pay attention to grade three toxicity, we know that's going to be different here, let's look at dead and almost dead grade four and five and see if that's different. And it really struck me when I looked at the deltas on the advantages, the clinical outcomes, and the deltas on the toxicity that, is this really worth it? Should this become a new standard of care? New England Journal usually doesn't print things that it doesn't think are at least at risk for being the new standard of care. So, those folks out there who take care of lung cancer are going to have to figure out if this really reflects a new change and is that worth it.

Are You Overdosing Your Patients? [00:04:08] 

And really why I picked that paper, it's important, but, to me, it's all about dose. And I think we are overdosing people. I am old enough to remember that when chemotherapy was the thing that we needed to get to what we call the maximum tolerated dose. And this was how much could you give you all know what this means. How much could you give without bumping the patient off, because the principle was that more was better.

I want to reflect on this a little bit because we learned pretty clearly in some cancers, that was true, germ cell cancer, some leukemias, maybe adjuvant breast cancer, but that dose intensity mattered in those diseases. But let's look at adjuvant breast cancer, because when I was a junior faculty member here, we were doing bone marrow transplants in the adjuvant setting for stage two and three breast cancers. So, we were doing marrow ablative, myeloablative therapies because more was better. And if you know that story, you know that the people who were leading some of those papers out of South Africa ended up committing fraud. Their results were fraudulent, and many, many wo