New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
IMPRESS: Gefitinib/chemotherapy versus chemotherapy in EGFR-mutant NSCLC after progression on first-line gefitinib
3:58 minutes.
TRANSCRIPTION:
DR KRIS: So in this clinical trial there were patients with EGFR mutations who all had up-front gefitinib. At the time of RECIST progression, they then were decided whether or not to continue the TKI with chemotherapy or just give chemotherapy. And remember, everybody was progressing. And what they discovered was, to me, as expected: There would be no difference in response, because both arms got chemotherapy, and no difference in PFS, which there wasn’t. The interesting thing, though, there was some survival difference favoring the arm that got chemotherapy and not chemotherapy plus gefitinib. So how do you sort this out? First off, this scenario is really not what we do. We don’t automatically switch everybody to chemotherapy at the time of RECIST progression. We just had a discussion about the nuances of doing that. And I think Tony would be the first person to say that you don’t do that. So when you go back to the biology of this, when the cancer progresses, not every cancer cell has a resistance mutation in it. In fact, the vast majority of cells are probably still sensitive to the original drug. Chemo works. I mean, if there’s one take-home message from this, it’s that chemo works. In this case, it was cis and pemetrexed, but it clearly works. And if you have an effective therapy that’s controlling all the clones, then it really doesn’t matter. But you have to be very careful, though. And Tony made a good point in doing this trial. People were not off the TKI for a long period of time. They very quickly got chemotherapy. So how does this change my practice? I think I would continue the TKI until I saw that I had a response to chemotherapy, if that was my decision, to give chemotherapy, and then I would stop it. DR LOVE: So is that what you were doing before you saw these data? DR KRIS: No, no. I was routinely continuing both, not knowing where that sweet spot was. Remember this very clear phenomenon of flare. It’s probably less than — if you have less than 10% second primary, not second primary but second-site mutation mutant alleles, that that tumor is probably still predominantly sensitive to the first drug. So if you stop it, the cancer will grow. The patient will get sick. DR LOVE: Dave, how do you approach this question? DR SPIGEL: Yes. I don’t do that. I probably am different than Mark in that I never really kind of wholly subscribe to just keeping that drug going. And outside of a clinical trial, I routinely just change those patients to chemotherapy. This trial makes me feel better about that decision. I agree with Mark. There are still a lot of questions out there. All the patients we see don’t routinely fit the patients who would have gone on this trial. There’s still more that needs to be sorted out, but I think we’re probably shifting away from this idea of continuing the drug through every line of therapy. DR LOVE: What do you think about this idea — actually, I’ve never heard anybody express this — of just keeping the TKI going until they start to get better? DR SPIGEL: I think that’s interesting. I could see why Mark said it best, the “sweet spot,” where is one drug — where have its benefits been lost, and the next therapy’s picking up? It’s an interesting decision point. I don't know how you decide whether the chemo is carrying all the weight or not. That’s an interesting approach. DR KRIS: May I say, I don’t think, as long as people are responding, remember, it’s the chemo, because the drug can’t make you respond. Erlotinib can’t make you respond at that point. You’ve failed it already. You’ve progressed. So any response is to the chemo. Once you have a chemo response, I would stop it. |