Real-World Efficacy of Palonosetron Three-Drug Regimen for Highly Emetogenic Chemotherapy
Dr. Haffizulla: So, Dr. Schwartzberg, we know you’ve studied the real world efficacy of palonosetron-based antiemetic regimens. What have the clinical trials suggested about the ability of this particular drug, which is an NK1R antagonist, and dexamethasone to prevent chemotherapy-induced nausea and vomiting?
Dr. Schwartzberg: Right. So palonosetron is actually a setron 5-HT3 receptor antagonist. And that combined with an NK1 plus dexamethasone, that triplet regimen is what is in the guidelines to use for anti-emesis protection for highly emetogenic chemotherapy. So clinical trials have been run with triplet therapy, those three classes of drugs, and palonosetron among the 5-HT3 receptors is the most potent single one that’s on the market. It has a longer half-life and it has higher receptor occupancy, and when tested head to head against so-called first-generation 5-HT3 receptor antagonists, it was better.
So this sort of represents the optimal of the triplet therapy. Now we’ve seen it in clinical trial data and what we wanted to do was look at how it worked in the real world. So this was a prospective trial of patients who were receiving highly emetogenic chemotherapy, mostly AC-based chemotherapy or cisplatinum, which are the two common classes or regimens that are used for highly emetogenic chemotherapy.
And what we found was that in contrast to the clinical trial data, less patients in the real world had a complete response, a complete response meaning no vomiting and no use of rescue medication over the study period, which is broken into the first day acute and days 2 through 5, that’s sort of the period of risk. And although the triplet regimen did pretty well in the acute setting, it’s that delayed period, days 2 through 5, where even the triplet regimen, many, many patients had vomiting or needed rescue medicine, particularly in the AC patients, and we’ve known that for a long time. So the bottom line is this is a good regimen, but it’s far from perfect and we need to improve on even our best anti-emesis regimens that are in the guidelines.
Dr. Haffizulla: Well, that’s a very good point. And you know, you outlined that very well, the suboptimal control that you saw from these particular results. What are your recommendations for the clinicians viewing today on how to best manage highly emetogenic chemotherapy?
Dr. Schwartzberg: Well, first of all is to follow the guidelines. So this was guideline-compliant and consistent, but one of the surprising things we’ve learned when you survey what patients are actually getting out there, many patients are not even getting the triplet. And what this study showed was even when you give guideline-compliant therapy, there’s still room for improvement. There’s a gap there. So a couple of things you can do. You can add a fourth drug, olanzapine, which has been shown in studying four versus three to improve the outcome and reduce nausea, in particular, in the delayed phase, so that’s one option.
There are other options for combinations, other 5-HT3 receptor antagonists, long-acting versions of all the drugs and other NK1s that are available, so I think the most important advice to physicians is not be complacent about your patients. There are things you can do. They should get the right antiemetics to begin with and then be adjusted if they don’t have satisfaction.
Dr. Haffizulla: Well, that’s really…it gives great evidence to why you were studying this in the real world setting as well too.
Dr. Schwartzberg: Right.
Dr. Haffizulla: So those variations happen and people respond differently.
Dr. Schwartzberg: Exactly.
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