Practical Considerations With Nintedanib in Lung Adenocarcinoma

Transcript:Martin Reck, MD, PhD: Docetaxel and nintedanib have been approved in the European Union, and it’s widely used. I have personal experience with them in a couple of patients. I think it’s very important to know we do see side effects, but they are manageable. We do have the opportunity of dose modification of nintedanib, and we also do have the opportunity to maintain nintedanib if we are not able to go on with the chemotherapy with docetaxel. As mentioned before, the predominant toxicity is generated by the chemotherapy, not by nintedanib. So, if we do have the case that the patient is not able to tolerate the combination, one may consider to stop docetaxel and to go on with nintedanib as a maintenance approach.

Anders Mellemgaard, MD: When selecting a treatment for a patient in second-line, I think many things go into the considerations here. And when you think about docetaxel, it is a treatment that does have toxicity. First of all, you need to believe that this patient can tolerate docetaxel. And then comes the second consideration here: should we add nintedanib to the docetaxel treatment for this particular patient? Again, if we think about toxicity, we know that there is an increased risk of diarrhea and elevated liver enzymes. We would have to think about whether this patient had a history of problems that would make it a particular issue here or not. So, that would also mean something when we select treatment for a patient.

And then, as we have talked about previously, the interval from first- to second-line therapy is important. So, a short interval, clearly to me, indicates a good reason for adding nintedanib. When we used the combination of docetaxel and nintedanib, I think you can say that we see patients for whom we need to offer this same kind of supportive care that we offer to all our patients. We need to be aware of the adverse events they develop during treatment, and we need to teach the patients about what they can expect so that they will react to it in a proper way. And we need to support these patients as we go through treatment. But if we do that properly, most of these patients will actually tolerate this treatment. Only quite infrequently will we need to do dose reductions or even interruptions for this treatment.

Usually when adding docetaxel and nintedanib, we can start patients on the usual dose of docetaxel and the usual dose of nintedanib. In a few instances, I’ve had patients where I was a little bit concerned about adverse events, where I’ve actually started docetaxel first and added nintedanib with a second course of docetaxel, just to make sure that if this patient would develop toxicity, we were actually able to manage it in a proper way.

Dose reduction is also sometimes needed, and obviously with docetaxel, there are a number of series that a patient can tolerate. In most cases, that’s for 6 series of docetaxel, and then the docetaxel is discontinued. But nintedanib can be tolerated for a long period. And so, for those reasons, patients are kept on nintedanib until disease progression. I think the experience with nintedanib is that as long as we give it with docetaxel, we do see some GI toxicity in some patients. But once the patients have it as a single drug treatment after we have discontinued docetaxel, we see very little toxicity. Most of these patients actually have no real side effects at all.

Sanjay Popat, PhD: My personal approach to decision making in the second-line setting, when thinking about nintedanib in conjunction with docetaxel, is to look at the ideal target population. So, in patients who may have PD-L1 expressing less than 10%, we may be better off using docetaxel in conjunction with nintedanib, rather than immune therapy, to compound, particularly in those whose disease is rapidly progressing or who may have progressed within 9 months of starting first-line therapy.

In that setting, one would want to discuss this with the patient and make sure that they’re apprised of all the data, and prepare them for the nature of the treatment that may be ahead. Specifically, we need to counsel them. They may get a touch of diarrhea, but if they do, loperamide should be the compound used and they should have early access to that. And once one is ensured that the patient is up to speed with the potential toxicities, then really, the therapeutic combination is very straightforward to deliver in real life.

Transcript Edited for Clarity