DR BELANI: So with ECOG 4599, when the trial was done there was going to be a third arm where there would be no bevacizumab maintenance, but then subsequently it was dropped. And the conclusion was made that ECOG 4599 is a positive trial where they gave bevacizumab up front with chemotherapy and then bevacizumab in the maintenance setting. Without any definitive data of maintenance, that became the regimen of choice.
And then we did the pemetrexed maintenance study. The first one was without pemetrexed in the front-line setting. The second one as with pemetrexed in the front-line setting. And both studies showed that in the intent-to-treat population it was beneficial to a significant extent, more so in patients who had not received pem up front as compared to those patients who received pem up front.
So I think that not all patients are candidates for maintenance. Only those who have an ECOG performance status of 0 or 1 are candidates for maintenance. And based on the trial that we did with the 5.3-month difference in overall survival with the use of pem maintenance after platinum-based combination chemotherapy, one could say that it has a significant benefit. And the overall survivals have actually increased. But in patients who have an ECOG performance status of 2 or higher, I would not consider maintenance. So maintenance is not for all, but it is for that select group of patients who have a good performance status, who continue to take it. And there are lots of patients who are on clinical trials or off study getting maintenance for prolonged durations of time without any significant toxicity.
DR LOVE: So John, Mark talked about maintenance at this point in his mind. He feels that when it’s used — and I think that would be kind of the standard to use it — it would be single agent. Do you agree with that, or are there situations, for example, where you might use pem and bev as maintenance?
DR HEYMACH: Yes. I think I tend to take an approach similar to what Mark described, so, for example, if I start somebody with carboplatin/pemetrexed and bevacizumab and then you have a choice of the maintenance regimen there, you can certainly justify using pemetrexed and bevacizumab together, as in PointBreak. And I suspect PFS is — well, we don’t suspect. PFS is better there than with monotherapy even though overall survival isn’t improved. So if a patient is symptomatic from their disease, I might consider that. But most often, I’ll just go to single agent with bevacizumab. And very often, patients have a long progression-free survival period there with very good tolerability with bevacizumab alone.
Now, we don’t have a study that addresses what I’m about to say exactly, but what my common practice is, at the first sign of a little bit of progression, then I’ll often add back pemetrexed, if the feeling is at that point we haven’t really gotten the benefit of maintenance pemetrexed. At that point it’s really second line or early second-line therapy. But at least what I try to do in the first-line setting for nonsquamous is get the maximum benefit I can out of both bevacizumab maintenance and pemetrexed. And I’m using them more sequentially rather than combined now. Now that’s, as I said, it’s a little bit mix and match, because the data doesn’t address it perfectly.
The ECOG 5508 is really going to be an important study when that reads out for clarifying which of those is better.
DR LOVE: And just to clarify that trial, which I believe you’re the PI on, Chandra, what’s the randomization there?
DR BELANI: Yes. So it is the 4599 regimen, carboplatin/paclitaxel/bevacizumab up front, 4 cycles. If they have stable or responsive disease, they are randomized to single-agent bevacizumab, which the control arm as was done in 4599, or single-agent pemetrexed or the combination of pemetrexed and bevacizumab.