New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Erlotinib and bevacizumab as first-line therapy in patients with advanced nonsquamous NSCLC harboring EGFR mutations
4:16 minutes.
TRANSCRIPTION:
DR KRIS: It was quite a simple trial. And what they looked at, the improvement in PFS by adding in bevacizumab to erlotinib up front, they found a very impressive improvement, a significant one. It makes a lot of intuitive sense to me to do that. We sadly know that our EGFR targeted therapies are sadly destined to fail. So to add other drugs in makes some sense. They also saw an extraordinary tolerance to the drug. I believe they gave a median of like 16 or 17 cycles, which is really pretty amazing. And it appeared to have a very good benefit. So I routinely do that off study now. DR LOVE: And if you look at the PFS table in the paper, I guess the hazard rate’s 0.54, just by adding bev. DR KRIS: The other thing that was pointed out to me is that the absolute improvement in PSF, PFS is double what the Sandler trial was. That has changed practice. DR LOVE: Yes. Interesting. Dave, how has this approach affected your practice? Have you used this regimen before the paper or since the paper? DR CARBONE: So actually for many years, if I have a patient who’s on erlotinib who has a nice response but then has slow progression, I’ve added in bev. And I’ve seen, most of the time, second nice responses that are relatively durable. And I think that’s a different question. But adding it up front, we have a clinical trial that’s asking that question that’s ongoing right now. And so my preference for first line is to put them on that trial, because I do believe that this is an active combination. DR LOVE: Corey, I ran into John Heymach, from Anne’s place, at ASCO. And I said, “Wow! Did you see that paper?” He said, “Oh, yes. We’ve already known that EGFR-mutant tumors are very vascular,” et cetera. What do we know about the biology of this, why it might be happening? DR LANGER: Why? That’s one theory behind it. Remember, even in unselected patients the combination in second line resulted in a PFS benefit, although we did not see a survival benefit. And in defense of those of us who have not routinely added bevacizumab to a TKI up front, you’re bringing people in every 3 weeks for IV therapy. You’re dealing with potentially additional toxicity. And again, until I see a clear-cut survival advantage, I’ve been a bit hesitant, although I have to confess, a hazard ratio of 0.54 with a 6- to 7-month improvement in PFS is quite impressive. DR LOVE: What about this idea of, in patients doing well, they’re stable but they’re objectively — we’re going to talk about that later, but one of the options, what about adding bev? DR LANGER: In the absence of either radiographic or symptomatic progression? DR LOVE: No, I’m saying the patient’s progressing. They’re stable. Their imaging is progressing. Have you done that, or would you do that? DR LANGER: I have done it, and I certainly would do it. DR LOVE: Have you seen responses the way Dave has? DR LANGER: I’ve seen stability after prior progression. I haven’t seen a dramatic response. DR LOVE: And again, just to poll the group: Anne, have you used up-front bev and an EGFR TKI? DR TSAO: I have not. I do what Dave does, which is add the bevacizumab into the erlotinib after they have some slow progression. DR LOVE: So Jeff, have you tried it? DR OXNARD: I’ve not. My concern about the data is, I’m worried the control arm underperformed. A PFS of 9.7 months in a trial that excluded brain metastases actually might be lower than we’d expect in a nonbrain met population. No treated brain mets allowed on this study, and so I still would like this to be validated in a second study before I use it routinely. DR LOVE: Dave, have you done it? DR SPIGEL: Have not. The Phase III is in progress now. DR LOVE: Same design? DR SPIGEL: Same design. DR LOVE: But you haven’t done it outside a trial? DR SPIGEL: Have not. DR LOVE: Mark? DR KRIS: I would do it in anybody who doesn’t fit a clinical trial. Particularly with a brain met, by the way. |