Ramucirumab in Relapsed/Refractory NSCLC

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.