Ronald J. Scheff, MD: I think that the REVEL trial is very important and informs my practice greatly. It’s an interesting trial. It makes use of ramucirumab in combination with docetaxel compared with docetaxel alone. Ramucirumab is an antibody that targets the VEGF2 receptor as opposed to bevacizumab, which targets VEGF itself. They’re both targeting the same pathways, and interestingly—but maybe not surprisingly—they’re both active in lung cancer and the toxicity profiles of both drugs are fairly similar.
The one reason I think the REVEL trial is so important is because it established the role of ramucirumab in combination with docetaxel in the second-line setting across many different patient types. To be in the study, patients could have any histology of non—small cell lung cancer. Squamous cell patients were not excluded, so that’s very clinically useful in our practices, because we’re seeing patients with all types of non–small cell lung cancer. Ramucirumab with docetaxel is indicated for all the different histologies. In the trial, what was also notable was that approximately 14% of patients in both arms had had bevacizumab as part of their frontline treatment. So, they were not naïve to anti-VEGF therapy and yet they also showed a benefit with the addition of ramucirumab to docetaxel.
It’s noteworthy that a quarter of the patients in the REVEL trial had received taxanes as part of their frontline therapy. Now, this is something we knew: The taxanes are not cross resistant. A patient who receives Taxol—for instance, paclitaxel—in the first-line setting may respond to docetaxel in the second-line setting. What I think is remarkable and useful about the REVEL trial is how generalizable it is. I consider the use of ramucirumab in combination with docetaxel in all types of patients who are in the second-line or third-line setting for non—small cell lung cancer. It’s for all histologies, regardless of what therapies they may have received previously. That’s what’s so exciting, in my opinion, about ramucirumab. It’s effective across different patient types.
Benjamin P. Levy, MD: Unlike bevacizumab, there were a proportion of patients in the REVEL trial who had squamous histology. That’s important because this drug is approved both for adenocarcinoma and squamous cell when patients’ tumors are progressing on a frontline regimen. How do I use this regimen in my practice? Certainly prior to the I-O blitz, or immunotherapy coming into the treatment realm for non—small cell lung cancer, I was using this in the second line. If patients were on a platinum doublet receiving maintenance Alimta [pemetrexed] or maintenance pemetrexed and bevacizumab when their tumors progressed, this is when I was using docetaxel and ramucirumab. I think we have to remember from the REVEL trial that not only were there squamous cell patients on the induction regimen allowed in the trial, but there were also patients who had received bevacizumab, and these patients also garnered a benefit from ramucirumab.
In my practice now, things have changed a little bit with the implementation of immunotherapies and checkpoint inhibitors firmly cemented as second-line therapy for most patients. That oftentimes moves docetaxel and ramucirumab, if not on a clinical trial, to the third-line setting. My sequencing strategy is that off of a clinical trial, patients generally get a platinum doublet up front with or without bevacizumab or with or without pembrolizumab, depending on the patient. When those patients’ tumors grow, we consider immunotherapy if they haven’t had pembrolizumab in the induction regimen, and after immunotherapy we then consider docetaxel and ramucirumab.
I’d say for the most part, docetaxel and ramucirumab is now a third-line option. However, there is a group of patients that I would consider for docetaxel/ramucirumab rather than immunotherapy in the second line. This is born out of the subset analysis from the REVEL trial that showed patients who were rapidly progressing on a platinum doublet derived a meaningful improvement with the addition of ramucirumab to docetaxel versus docetaxel alone. Because of that, I think patients who are rapidly progressing may have a preserved performance status, and are PD-L1—low patients for whom you may want to consider docetaxel/ramucirumab rather than I-O therapy.
Ronald J. Scheff, MD: Treatment sequencing becomes an increasingly interesting and important aspect of managing non—small cell lung cancer because we have so many options. I certainly think, based on clinical trial data in the first-line setting for patients who have a tumor proportion score for PD-L1 that’s high, that those patients are going to start with immunotherapy first line. Typically, I use a platinum doublet in the second-line setting. In the third-line setting for those patients, I would typically use a docetaxel and ramucirumab regimen. For patients who receive chemotherapy in the first-line setting, it’s an interesting choice in the second-line setting between immunotherapy, which is a choice I commonly make, and ramucirumab with docetaxel, which is also a very valid regimen for the second line. Whichever of those regimens, immunotherapy or docetaxel and ramucirumab, that I did not use in the second line, I would typically use in the third line.
Ann Tsao, MD: In my practice, if I’m giving an antiangiogenic agent in the frontline setting and they have benefit, I will still consider using ramucirumab in the second line setting. If this is a patient who is benefiting from this class of drug, giving them an additional class of drug in the second-line or third-line setting may be beneficial.
Transcript Edited for Clarity