The REVEL Trial and Subanalysis

Anne Tsao, MD: The REVEL trial was a study done prior to the immunotherapy era. And this was looking at docetaxel versus docetaxel plus ramucirumab, which is an IgG1 monoclonal antibody to the extra cellular domain for VEGFR2. And what it showed was that the combination of docetaxel and ramucirumab was superior to docetaxel for progression-free [PFS] and overall survival [OS]. So it definitely got accepted as a salvage second-line therapy. And the nice thing about this is it was accepted for both patients with adenocarcinoma as well as squamous cell carcinoma. So all histologies.

Now, again, this was done in the era before immunotherapy. So we don’t really have much data yet about what happens after you’ve given immunotherapy or an immunotherapy-chemotherapy combination, and what the data would be with docetaxel, ramucirumab. However, we do think that this is an effective regimen and that it may also, because of subset analyses, be quite effective in patients who have rapid progression after their front-line therapy.

Benjamin Levy, MD: The REVEL trial was 1 of the largest second-line trials we’ve had. More than 1000 patients were randomized to docetaxel versus docetaxel plus ramucirumab, an antiandrogen as a strategy. And we saw from that trial a meaningful benefit in overall survival. I think what we’ve further learned and have gleaned some significant insight from some subset analyses. And if we looked at patients, remember, this is a second-line trial, but if we looked at patients who had what we call rapidly progressing disease on the first-line induction regimen. Prior to them receiving the docetaxel or the docetaxel-ramucirumab, these patients also derived a meaningful benefit in overall survival with the addition of ramucirumab.

Anne Tsao, MD: The subset analysis from the REVEL trial, looking at patients and how quickly it progressed and what their responses were to the ramucirumab-docetaxel versus docetaxel, I think, is very thought provoking. Again, it was an exploratory subset analysis, but it did show that patients who have rapid progression do benefit from the combination of docetaxel-ramucirumab. So if I do have a patient who progressed rapidly after the frontline treatment, I definitely have used in my practice the docetaxel-ramucirumab and have been able to reestablish control in some of my patients.

So I think that this is a very viable and reasonable salvage therapy in our patients. Again, we do need more data about what happens after immunotherapy, but for right now it is something I am doing in my clinical practice.

The REVEL trial was actually conducted in the second-line setting for any histologic subtype. And it showed a superior PFS and OS across all the histologies. So docetaxel-ramucirumab can be safely given in any histologic subtype.

Although the REVEL trial was a second-line trial, I admit that I have done it in third line and sometimes even fourth line. And so this is a very reasonable regimen. You can get it second line and above in our patients who have progressed from a frontline regimen.

Roy Herbst, MD, PhD: Based on REVEL, docetaxel with ramucirumab was shown to be superior to docetaxel alone, both in the squamous and nonsquamous patients. So I don’t worry about tumor type. I would use it in both. It produced a survival benefit in the 0.8 range. It wasn’t the biggest benefit in the world but it was better, and it also was shown to be safe and concerns in the squamous patients with bleeding were unfounded. So that is the standard of care. It sometimes isn’t used as much as it could be because its approval occurred just as immunotherapy was coming through, and everyone is very interested to use immunotherapy. But now that immunotherapy has moved to frontline, we need to have second-line options. Patients come in with a good performance status, and there are things that we need to do for them. So I think that’s very important.