The Role of Anti-Angiogenic Therapy in Lung Cancer - Episode 4
Ramucirumab is another anti-angiogenic agent. It’s a monoclonal antibody that is directed at the vascular endothelial growth factor receptor 2 (VEGFR2), so it’s a receptor-based antibody which is distinct from bevacizumab, which is a ligand-directed antibody. The REVEL trial tested ramucirumab in the second-line setting of metastatic non-small cell lung cancer.
This trial randomized patients to either docetaxel as a control arm or the combination of docetaxel plus ramucirumab. The ramucirumab was given every three weeks along with the docetaxel. Interestingly, in this trial, they included both squamous and nonsquamous histologies. Squamous is a no-no with bevacizumab because of the risk of pulmonary hemorrhage, and so we exclude patients with squamous histology for the use of bevacizumab in the first-line setting. But they did not see that same signal of safety with regard to ramucirumab. So squamous patients were included, which I think is a strength of ramucirumab because it’s not histology-dependent; it includes all histologies.
In the REVEL trial, there was an improvement in overall response rate from about 13% to about 22% with the combination. There was a significant improvement in progression-free as well as overall survival, with a hazard ratio of approximately 0.86 or so in favor of the combination of docetaxel and ramucirumab. As expected, there was an increase in toxicities that we would expect from anti-angiogenic therapy; hypertension, some bleeding, hemoptysis, and those sorts of things. This is not a surprise with the use of an anti-angiogenic agent. None of these toxicities were prohibitive and, I think, like bevacizumab, with proper patient selection, ramucirumab is a safe addition to docetaxel in this particular setting.
The achievement of the primary endpoint of overall survival in the REVEL trial led to the FDA approval for ramucirumab in combination with docetaxel in December of 2014. This was actually a very important milestone to reach because bevacizumab has been approved for a decade or so in the first-line setting, but we did not have an anti-angiogenic strategy beyond first-line that we knew was effective in improving overall survival. That was achieved in the REVEL trial, and now ramucirumab is an option for patients.
We have had, over the past year, a lot of change in the second- and third-line settings with the approval of a couple of immunotherapy agents. So there are significantly more choices for patients, and one of the challenges is deciding the order of treatment for these particular patients. Honestly, I think that it’s in a bit in flux at this point, and we need some further data to help us put the right treatment in the right spot for the right patient at this particular time. But the addition of ramucirumab as one of our choices added to docetaxel is a clear advance for our patients with advanced non-small cell lung cancer.
Transcript Edited for Clarity