Antiangiogenic Therapy: Appropriate Therapeutic Options and Sequencing in NSCLC - Episode 10

Key Points From the REVEL Trial in NSCLC

Benjamin P. Levy, MD: The REVEL trial looked at adding ramucirumab to docetaxel compared with docetaxel alone for patients with stage 4 adenocarcinoma or squamous cell histology, who had progressed on platinum chemotherapy. Some of these patients received maintenance if they were doing well, but this a second-line trial. Importantly, in the frontline setting, a percentage of the patients had received bevacizumab. Those patients still garnered a benefit with ramucirumab added to docetaxel.

In this trial, the bottom line was that adding ramucirumab to docetaxel improved response rate, progression-free survival, and overall survival. I would make the argument that we’ve tried, very hard, to add novel agents to docetaxel to try to get a survival advantage. We have failed, a large percentage of the time. This was one of those few exceptions, where adding ramucirumab, an antiangiogenic drug, to a docetaxel backbone improved survival.

I would argue that any survival advantage is meaningful. Does that mean that every patient who’s on platinum-doublet chemotherapy, who progresses, gets docetaxel with ramucirumab? No. But given that we now have immunotherapy moving upfront with chemotherapy, I do think we need to look hard, to really try to generate some data to see how docetaxel/ramucirumab performs in these patients. Outside of the clinical trial, I think that this is kind of my de facto regimen, if they can tolerate it.

I think patients need to be exposed to every single drug possible in a short amount of time, especially if their tumors are growing rapidly. This is a regimen that should be considered for patients who are progressing on platinum-doublet therapy.

We need to keep in mind that the REVEL trial included both adenocarcinoma and squamous cell patients. Both of these patient populations, if they are progressing on a platinum-doublet regimen, are candidates for ramucirumab with docetaxel. For both of these patient populations, if they are progressing on a platinum-doublet therapy with or without immunotherapy, I will consider using the doublet for a fit patient. If they’re not fit, maybe I won’t add the ramucirumab. But if they’re fit and motivated, then I try.

The question becomes, if you haven’t used immunotherapy with chemotherapy upfront, and you’ve instead used it as a second-line option, what do you do in the third-line setting? This is where things get a little tricky. The docetaxel/ramucirumab regimen really just looked at the second-line setting. For patients who start out on carboplatin/pemetrexed, who then go on to receive immunotherapy, what do you do as third-line therapy? That patient population may be a little harder to deliver ramucirumab with docetaxel in, but it’s something that I try to do if they’re fit. I may move, at that point, to a weekly docetaxel regimen with ramucirumab, but I wouldn’t not consider it just because we’re at the third-line rather than second-line setting. I try to give the best drugs to the patient that I know work at the line of therapy in which they need it.