DR SPIGEL: This was an attempt really to look at the data that have already come out with crizotinib and see how effective could this drug be in treating patients with brain metastases. So this as again another retrospective analysis from the pivotal crizotinib studies to date (Proc WCLC 2013;Abstract MO07.02), actually looking at a fair number of patients. So there were a little over 100 patients who had brain metastases at baseline. So these are patients that have not been previously treated for brain metastases. For about 160 patients who had previous treatment for brain metastases, and then there were about 600 patients they looked at who had no history of brain metastases at baseline. And the goal here was to see in these 3 groups who got crizotinib, how did they do.
The group of patients who had previously untreated brain metastases who received crizotinib, there was a 56% so-called disease control rate that included intracranial lesions. The response rate of the intracranial lesions was 7%. In the 160 patients who had previously treated brain metastases who then went on to crizotinib, who had progression in their disease, in their brain, there was a 62% disease control rate, again with a 7% response rate. So what this suggests is that if you have brain metastases at baseline, even if they’ve been previously untreated, there is a chance, maybe better than half, that crizotinib alone could control that disease for some period of time. A small number of those patients will actually have shrinkage in their tumor.
Kind of intriguing, not exactly a prospective analysis of how effective crizotinib would be at controlling brain metastases, but suggesting that maybe like with erlotinib, this would be a reasonable strategy for some patients.
DR LOVE: So I don't know, Greg. Maybe more details of the study would be more illuminating, but the numbers that you just talked about — because, like, disease control sounds a little bit like stable disease to me. And when I think about, for example, an EGFR TKI, I think about those things shrinking down in the brain. Does that sound like the same thing’s going on here with crizotinib?
DR RIELY: No. I don’t think so. I think that data support the idea that there is some activity of crizotinib in the brain.
DR RIELY: But I feel like it’s inadequate, so that if I see up front a patient with ALK-positive lung cancer and they have brain metastases, I may decide to treat them with crizotinib as initial therapy, but I’m not going to have the same comfort level. And I would strongly weigh the idea of initiating whole-brain radiation prior to starting crizotinib.
DR LOVE: That’s really helpful. Again, I can remember a bunch of emails I’ve gotten over the last couple of years about this. And again, I’m not sure that I’ve had this on my radar, Ram, exactly. So what I’m hearing from you all is that maybe there’s not as much data to support using, as Greg just said, systemic therapy, crizotinib or whatever, in a patient with a brain met, as in a patient with an EGFR mutation?
DR GOVINDAN: That’s probably true. But I also want to point out one more paper that was published in the Sydney meeting on afatinib in patients who had brain metastasis, EGFR mutant. This was actually an analysis from the LUX-Lung 3 study. That, you may recall, was a randomized study comparing pemetrexed/cis with afatinib in EGFR-mutant patients. That study met the primary endpoint of better progression-free survival with afatinib. There they went back and looked at the 35 patients they had with brain metastases. That study allowed patients who had stable brain metastases. So this is one of the rare opportunities for us to look at what happened in a prospective trial, because conventionally the prospective trials exclude patients with brain metastasis.
So the bottom line is the group of patients who had EGFR mutation, brain metastasis at presentation, did about as well as the other group without brain metastasis (Proc WCLC 2013;Abstract MO07.13). The benefit for afatinib was almost the same. And in a very small number they had data on the time to CNS progression, and these were investigator assessed, one. And there’s about 11.6 months with afatinib, just 7 patients, and about five and a half months with chemotherapy. And so all these things point to the fact that if you have a sensitive disease, if it’s the brain, if it is not a large disease, stable, clinically not very symptomatic, it’s okay to start them on these small molecules to begin with. And, of course, you have to watch them closely.
DR LOVE: But globally at this point and hopefully, for sure, we will have more data in the future. Do you kind of agree with the thought that maybe the ALK situation is not as favorable to using systemic therapy, or is it really too early?
DR RIELY: I would clarify that to say not the ALK situation, the crizotinib situation.
DR LOVE: The crizotinib. Okay. That’s true. We should get into that in terms of these other agents. But in terms of crizotinib and brain mets, this concept of in a stable patient, do you agree with Greg that you’re less likely to do it with crizotinib than, say, with an EGFR TKI, less confident, or not necessarily?
DR GOVINDAN: I don’t think we have as much data. We have seen anecdotally these patients respond well with EGFR. And maybe it’s a function of time. And especially that issue may be totally relevant or may even be more favorable in the ALK patients with the new next-generation drugs, which have a greater penetration, greater activity.
DR RIELY: But what do you do?
DR GOVINDAN: So today, if I have a patient with ALK-positive non-small cell lung cancer with a brain lesion, I probably would take the safer approach to stereotactic radiation and then start them on crizotinib.