New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Predictive value of the VeriStrat assay for patients with NSCLC treated with second-line erlotinib or chemotherapy
5:09 minutes.
TRANSCRIPTION:
DR LOVE: So David, I was fascinated just by the fact that there was a Phase III trial looking at a biomarker to start with. You just don’t see too many studies like that. The PROSE study was published in Lancet Oncology. Can you kind of review what was seen there and what you think about it? DR CARBONE: So let me just back up a second, when Mark said why use a targeted therapy without a target. I think it’s very clear that some tumors still have some EGFR signaling dependence even without the mutation. But I think it’s also very clear that EGFR mutation is by far a stronger biomarker than anything else we have in the wild-type setting. And if you look across multiple studies, there’s clear small benefit in the population. But it looks like the population is divided into people who do really poorly on erlotinib and those who have stable disease or do okay. And the VeriStrat test was something that was developed to try to segregate those 2 populations. Even if you look in, say, the IPASS trial with gefitinib versus chemo, there’s a rapid drop in PFS in about half the patients. And then the rest of them just trickle on in a very similar — if you eliminated this initial drop, the PFS of that second half is similar to that on chemotherapy. So this test was developed, it’s a proteomic test in peripheral blood that was designed to try to identify which patients should not get erlotinib, which patients should in a wild-type setting. So this was a trial in second-line lung cancer where patients were randomized between erlotinib and standard-of-care chemotherapy. It stratified for this VeriStrat test. And what it did show is, it confirmed that a subset of patients did very poorly on the erlotinib in the VeriStrat poor situation and that patients treated with erlotinib, when VeriStrat good, did just as well as with chemotherapy. And the trial was designed to look at an interaction p-value, a predictiveness assay/test, and it was statistically significantly predictive for that interaction test, and, thus, the conclusion is that if erlotinib is chosen, then it’s reasonable to do this test to segregate those people who should get erlotinib versus chemotherapy. And, in fact, I think it just made the NCCN Guidelines in that setting as well. DR LOVE: So can you describe a clinical situation where you would use this assay, David? DR CARBONE: The best situation would be in somebody who’s progressed after doublet chemotherapy and you’re trying to choose between — has no targeted therapies available and there’s a number of second-/third-line options available, all of which have minimal benefit in a patient who may live far away, where intravenous therapy is inconvenient. I think if they were VeriStrat good, then erlotinib therapy in that patient would be an option. DR LOVE: So Dave, you see a lot of patients who are far away from you. What do you think about that clinical scenario? DR SPIGEL: I was just kind of laughing at that, as the list got narrower and narrower in David’s description. I don’t use erlotinib second line. I do think it’s a reasonable option third line for patients who’ve had 2 prior lines of chemotherapy and have had enough of the needle and like the idea of coming in once a month. And I think we all have those patients. For me, it’s been squamous patients who ride this out for 6 or 8 months. And it’s probably the easiest thing that they’ve done in their 3 lines of therapy. One can make an argument in that setting, this study doesn’t apply, because this was a second-line trial. So in a third-line setting, would the data have come out the same way? So I don't know. I’ve ordered the test once. Actually, William Pao and I shared a patient from Vanderbilt. And William actually — I talked about it. We got it in the gentleman. He tested in a good group, so to speak. And so he did well on erlotinib. But I haven’t ordered it since. And I think if I was looking at a second-line setting, making a decision, as David pointed out, I could see its value. And it’s impressive. It did get published in a peer-reviewed journal despite the criticisms at ASCO when it was presented. |