Transcript:Shreyaskumar Patel, MD: In terms of tolerances, I educate my patients and tell them up front that they will need to be on the lookout for this and guide me as to, is this treatment working out for them or not? Because there are patients who will tolerate the more serious toxicity in a pulsed manner as opposed to this chronic low-grade toxicity, and there are patient populations for whom one works better than the other. That may be another way to personalize which is the right treatment for whom.

William D. Tap, MD: That’s a great point. So, Martee, you spoke a little bit about trabectedin, too, and I think we can take a transition to this. George, this is a drug you personally championed in the United States. And Martee was involved in the trial, right?

George D. Demetri, MD: Since1997. Exactly. It’s been a research drug longer than many people have been alive.

William D. Tap, MD: What has been this passion? Talk to us a little bit about trabectedin.

George D. Demetri, MD: Trabectedin is a fascinating drug. First of all, it’s got a beautiful molecular structure. It comes from a beautiful marine creature, this colonial organism, and was extracted and was shown preclinically, back in 1997 or so, to have extraordinary activity against many kinds of sarcoma cell lines. Now we all know that sarcoma cell lines can lie to us, even if you’ve got a picomolar, very low sensitivity. It may not work in humans. But then, some of our European colleagues tested it and some of the European patients had extraordinary responses, which is very rare. What was extraordinary about it is that they lasted years continually taking the drug. So, that, I think, is why our whole community has stuck behind this very difficult development plan through a long time. It is actually good to finally walk that particular football over the goal line and finally have the FDA really say, “Okay, that’s enough data. We believe that this is good for patients.”

I think what was interesting about it is that we still don’t know exactly what mechanism is responsible for it working in the patients with metastatic disease who get 4 and 5 years of benefit out of taking this drug. It’s also all about having rational expectations set up to the patients. This drug is potentially dangerous if you don’t have experience with it. And I always counsel outside doctors to be careful with this one. It is a vesicant. It’s given by 24-hour continuous infusion. Unless you have great nurses like we have, with a lot of experience, it can be difficult to really know how to put it into the ports. It has to be given through a central line, so it’s very irritating to the patients.

But once a patient gets the hang of it, they can come in, get the bag, go home, 24 hours later come back in, get disconnected, and have a pretty darn good quality of life. Because we do have these younger patients that are healthy and for whom they’ll go out and exercise too much, literally, while they’re getting the 24-hour infusion. It doesn’t have a lot of other side effects in many patients. But it has to be done by somebody with some experience. So, I always caution the community about that.

William D. Tap, MD: Martee, I know you have good experience with this drug being involved in the phase III study, too. What are your thoughts?

Martee L. Hensley, MD: Well, I think that it was an exciting drug for people to have access to. Already, the patient community knew about trabectedin. They knew that it was available in Europe, for example, and people were really clamoring for access in the United States. So, when the randomized trial became available, it was exciting for me to be able to put patients on the study. For the patients getting trabectedin, you need to know what you’re doing. But already, I work in a center where we’re used to using infusion pumps. Maybe not so much for sarcoma treatment, but for other cancers. And patients really almost felt empowered by that ability to be getting a drug at home, but also reassured by coming back the next day to say, “Oh, I got my drug and I’m successfully unhooked.” So, there was a real acceptance of it. I do set expectations that objective response rates by RECIST are low, but that disease control rates can be very long.

Transcript Edited for Clarity