Transcript:Mark A. Socinski, MD: Eddy, I was going to go to you first. You led the REVEL trial. It led to an FDA approval for ramucirumab in the second-line setting. Can you kind of walk us through that trial and tell us your thoughts on it?
Edward Garon, MD: Sure. Of course, there were many investigators throughout the world, about 1200 patients. Maurice Pérol, in Lyon, France, was also very involved and presented the data at ASCO. So, the study was a phase III study trying to demonstrate that docetaxel/ramucirumab was a superior treatment option with a primary endpoint of overall survival as compared to docetaxel. And, docetaxel, really had been the mainstay of second-line therapy, at least in clinical trials, for well over a decade by that point. This was based on a fairly unimpressive response rate and fairly poor; in fact, overall survival and progression-free survival. It was sort of a standard of care that people, in many respects, weren’t that thrilled with. But nothing had really beaten it for this non-EGFR, non-ALK gene rearranged, which is the great majority, of course, of what we see in non-small cell lung cancer. So, patients were randomized to docetaxel with either ramucirumab or placebo, and, again, this was a global study. Patients were allowed in if they had squamous histology as well—which, as was mentioned earlier, had been a contraindication to use of bevacizumab to date.
And, the goal was to evaluate overall survival, and what was shown was that there was, in fact, an improvement in overall survival. One question in addition to whether it would improve survival is with regard to tolerability. The tolerability overall looked quite good. There was no evidence of some of the things that we were certainly worried about going into the study. So, bevacizumab was not developed in squamous cell carcinoma because early on in clinical development there was some data regarding hemoptysis—which was, in many cases, fatal—that was associated with its use. This study did allow patients with squamous cell carcinoma, although excluded patients with particularly central tumors. But, we did not see a difference in terms of complications of pulmonary hemorrhage and hemoptysis between the two groups. And the results also looked quite similar by histology—both in squamous and non-squamous, non-small cell lung cancer.
There also was a recently published quality of life analysis showing that there really was not a decrement in quality of life with the addition of ramucirumab. I think those would be the take-home points. The response rate was increased. The response rate actually was upwards of 20%.
Mark A. Socinski, MD: Almost double.
Edward Garon, MD: Yes, and it’s interesting. Going into the study, our assumptions about response rate and even progression-free survival were, in many ways, exceeded as part of the study. And it was exceeded actually in both arms.
Mark A. Socinski, MD: Both arms, yes.
Edward Garon, MD: Both the placebo arm, as well as the ramucirumab arm, but there were clear differences with improvement in response rate, progression-free survival, and overall survival in the ramucirumab arm.
Mark A. Socinski, MD: It was one of the few trials where you get the trifecta, right? You get OS (overall survival), PFS (progression-free survival), and overall response rate, and really no new safety signals with that drug.
Transcript Edited for Clarity