Corey J. Langer, MD, FACP: The REVEL trial showed a significant advantage for combining ramucirumab with standard second-line treatment—at that time, docetaxel. What’s interesting about this trial is that the benefit was seen not only in the second-line setting but in both nonsquamous and in squamous cell patients. If you remember, bevacizumab is approved only in nonsquamous disease. So, for a year or two, it became our standard of practice—docetaxel plus ramucirumab. Then immunotherapy data emerged in the second-line setting. As a result, because immunotherapy looks so much better than docetaxel, there was collateral damage to ramucirumab. It was paired with docetaxel. And so that combination was really relegated to the third-line setting.
Now, with the emergence of immunotherapy in the frontline setting, it is being reintroduced into the second-line setting in a patient whose disease progresses on combination chemotherapy with one of the checkpoint inhibitors. So, for a while, I wouldn’t say that I had stopped using the combination, but I certainly reduced my use. And with the emergence of KEYNOTE-189, I clearly increased my use. It’s a tough regimen, and it has nothing to do with the ramucirumab. It has to do with the partner agent— docetaxel. In Japan, the docetaxel dose is typically 60 per m2. In the rest of the world, in North America and Europe, it’s 75 per m2. The survival benefit is seen regardless of the dose. I just find that the 60 per m2 dose is an easier dose to use, and I have really gravitated toward that dosing.
As time goes on, I think we need to reinvestigate how we treat patients in the second-line setting. In individuals who were treated in KEYNOTE-189, who have been on maintenance therapy for a while—3, 4, or 6 months—who then experience disease progression, there’s no reason in the world not to reintroduce a platinum. Those patients may be just as sensitive to platinum as they were at the beginning.
We’re about to embark on a clinical trial looking at carboplatin with a weekly taxane, either nab-paclitaxel or conventional solvent-based paclitaxel, combined with ramucirumab. I believe that these types of trials will increasingly be started, particularly in this unique setting that has been generated by the adoption of immunotherapy in the frontline setting.