DR BELANI: So PointBreak study looked at the investigational arm of E4599 as the control arm.
DR LOVE: So that’s carbo/paclitaxel/bev. Followed by bev.
DR BELANI: Carbo/paclitaxel/bevacizumab followed by maintenance bev. And then the second, investigational arm of the study was carboplatin/pemetrexed/bev followed by pem/bev as a combination. So actually there are 2 variables in the study that in the front part it is pem instead of paclitaxel but in the second part, also, there is additional pem in addition to bev. So actually it — if there was a third arm without bev, then I guess the study would have been more definitive. If it was carbo/pem followed by pem alone, that study would have been more informative as compared to the trial as said.
So these 2 arms of the study, it was powered as a superiority trial. And the trial did not meet its endpoint of superiority and, actually, numerically in terms of overall survival, the carbo/pem/bev followed by pem/bev was numerically inferior but not statistically different. So if you look at the numbers, the median survival of the pem arm was 12.6 months versus 13.4 months for the ECOG 4599 arm of the study.
DR LOVE: So Mark, I’m kind of curious — you’ve been involved in the middle of the PointBreak study — what your global take on it is and starting to get into the issue of what you do in your own practice. What would you say to this oncologist — 2 minutes about what the key takeaway here is and what it means to clinical practice?
DR SOCINSKI: I mean, one of the big advances in adenocarcinoma or non-small cell lung cancer therapy was ECOG 4599, adding bev to our old favorite, carbo/paclitaxel. At the same time, we have the sense, based on the Scagliotti data, that pemetrexed actually is a better drug, at least better when compared to gemcitabine. Okay? I was never convinced that it was necessarily better than the taxane. We had Phase II data from Dr Patel, small Phase II trial, carbo/pem/bev followed by pem/bev maintenance. That looked encouraging, more encouraging to some, less encouraging to others. But it kind of set up the PointBreak trial, which, as Chandra points out, correctly, it’s really in the first 4 cycles is pemetrexed more active than paclitaxel in a bev-eligible population? The answer to that is no. The response rates were 33% on both arms.
Does the maintenance strategy — we’ve had this excitement about maintenance therapy. Does the 2-drug strategy — we had both switch and continuation maintenance data come out with pem. Maybe that seemed like a good idea. When you look at the overall survival, there is no difference. Now, there’s a modest benefit in PFS in favor of the pem/bev maintenance versus bev-alone maintenance. And I characterize it as modest.
So how has this changed my practice? I use more paclitaxel when I give bev. I don’t do 2-drug maintenance. I do 1-drug maintenance. And I tend to use bevacizumab maintenance if I use bevacizumab first, because once you use or stop using bev, you can’t go back, essentially. Pem, since it has an indication in first, second and maintenance therapy, you have much more flexibility in terms of going back to that drug.
So in a wild-type population, what PointBreak means to me is paclitaxel/carboplatin/bev is a very good regimen. Pem doesn’t add to that. Maintenance strategy should be monotherapy strategies. And if you don’t use pem up front, it’s there as a second-line agent.
Now the one other thing is that it creates a different toxicity profile. There are some people who you don’t want to take the chance of neuropathy or have baseline neuropathy. There’s a fair amount of the population that has alopecia concerns. And so it creates flexibility in terms of what regimen you use in this particular setting. So there are differing toxicities and, I might add, financial toxicity to the pemetrexed arm, because that’s still an expensive drug, using it with another expensive drug. And sometimes that is occasionally an issue.