New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Potency and tolerability of emerging ALK inhibitors compared to crizotinib
2:56 minutes.
TRANSCRIPTION:
DR LOVE: Mark, any thoughts about this potential choice between alectinib and ceritinib? DR KRIS: I think there’s no good way to choose now. Again, I think if you adjust the dose of ceritinib you can get it to the same toxicity level that you can get with alectinib. And I think both drugs are much more potent. I think Jeff’s point earlier, there’s an issue here about specificity and potency. And these drugs surely are better. And again, there are other ones in the pipeline as well, as David said. DR CARBONE: Yeas. I just wanted to comment that this is a very crowded field. And I had a patient who had metastatic ALK-positive disease and progressed after only a few months on crizotinib. I actually sent him to Dave Spigel, and he went on the Pfizer next-generation drug. DR SPIGEL: 9322. DR CARBONE: And the guy, he’s a physician. And he said, “I really never felt good, even though I had a response on the crizotinib.” And he said, “I have no side effects from this drug and I feel terrific.” And he’s had a near-complete response in the brain and in his chest now lasting twice as long as the amount of time he spent on crizotinib. So we’re going to have a menu of these drugs available to us in the next few years, and it’s quite exciting that we’re not only seeing better efficacy, but we’re also seeing lower toxicity. DR LANGER: I think in the ALK field, perhaps in the EGFR mutants but certainly in ALK, we’re going to witness a change over the next 3 to 5 years where the second- and third-generation drugs may ultimately eclipse the first generation. DR LOVE: I was going to ask that. And Jeff, I’m curious about your thoughts about ceritinib versus alectinib. But also, getting back to what David was talking about earlier ultimately how to sequence things. Should the second-generation drugs be used before crizotinib or kind of, in the long run, would you be better with the crizotinib first? DR OXNARD: I think in the end, these will beat crizotinib because they’re better ALK inhibitors. And we’re not going to see that in EGFR, perhaps, but it’s going to happen in ALK, no question. I, too commonly, am disappointed with my crizotinib response and especially the brain problem. I mean, this is a real problem. We are struggling with control of brain metastases. And each of these drugs has the chance for greater potency. I do have a patient. I ran into him at an airport somewhere. He’s on full-dose ceritinib, looks like a normal guy. I mean, I have patients who do great on full-dose ceritinib. But for your community doctor who is not going to prescribe these drugs a lot and doesn’t have a lot of time to figure out how to dose them easily, I think a tolerable ALK inhibitor is, in the end, going to probably trump ceritinib. DR LOVE: And any sense in terms of alectinib versus ceritinib, if they were both available, how you would utilize them? DR OXNARD: I’ve seen toxicity on alectinib. I had a patient with elevated LFTs. But you see that with anything. And I would probably pick alectinib, based on the GI toxicity I’ve seen from ceritinib. |