Lung Cancer Update, Issue 3, 2016 (Video Program) - Video 13Case discussion: A 45-year-old man with ALK-positive NSCLC and brain metastases
3:22 minutes.
TRANSCRIPTION:
DR BLUMENSCHEIN: This is a gentleman who, again, presented with a brain metastasis. And during the course of his evaluation and treatment for his brain metastasis, found to have non-small cell lung cancer and it was ALK-positive. And we placed him on crizotinib just over a year ago, and he’s responded. He’s doing well. And he’s having nominal symptoms from his treatment and is actually living a very full life. And of the patients that I’m treating right now with ALK inhibitors, I’ve got a number of patients who are 3 years and 4 years on crizotinib, which I know is outside the bandwidth of what we consider the usual progression-free intervals. But in the event that he does develop progression of disease, there are a number of options now — ceritinib, alectinib — which are now approved, so he has a number of choices. But as long as he’s doing well, we’re going to continue with what we’re on. Now the other thing is, and this has been something that’s been documented, that patients with ALK translocation have higher rates of brain metastasis, approaching 40%, 50%, even 60%. And that’s likely a reflection of the fact that crizotinib doesn’t penetrate the blood brain barrier as well, and patients are staying on therapy for long periods of time allowing these metastases to develop. The nice thing about these subsequent generations of drugs, ceritinib and alectinib, is that they both penetrate the blood brain barrier and can treat brain metastasis. DR LOVE: So I want to ask you about particularly the first-line study that was presented at ASCO looking at alectinib versus crizotinib. But first, getting back to patients on crizotinib, this patient, as well as these other patients that you mentioned who’ve been on it long term, a couple of things I’m curious about in terms of what you see long term. Visual changes. I know a lot of people see that in the beginning. Does that continue, or what happens with that? DR BLUMENSCHEIN: So this particular patient has had some visual changes, more in the evening. But they’re nominal and not interfering with his activities of daily living. And they do wax and wane. DR LOVE: But they continue? DR BLUMENSCHEIN: Yes. He’s had this periodically throughout the year of treatment. DR LOVE: The other thing that I first heard about from Ross Camidge, and I don’t know how common it is, is hypogonadism, I think mainly in men. Have you seen that? DR BLUMENSCHEIN: I haven’t seen it. But it is a potential side effect or sequelae of the drug. DR LOVE: And finally, I’m curious about your thoughts about the study, the J-ALEX trial, the first-line study presented at ASCO comparing alectinib to crizotinib. DR BLUMENSCHEIN: No. So that was exciting data. I think we need data that’s more of a Western European population to make that assessment, though. It’s certainly promising. It looks like a more potent drug. And the question that’s going to come up is, what’s the best way to sequence these drugs? The second- and third-generation drugs worked on the mutations of resistance that patients who get crizotinib develop. So the question will be, is it better to give, say, alectinib up front, and then what are you going to do as subsequent therapies? Or is it better to go with crizotinib up-front and then you have a clear path of multiple therapies and sequential treatment? Where do you get the most mileage for the patients? |