Anti-Angiogenesis in NSCLC

Benjamin P. Levy: It’s very clear now that VEGF signaling and angiogenesis are critical factors for tumor growth. The recruitment of blood vessels and the development of new blood vessels within the tumor microenvironment and the vasculature, this feeds the tumor to grow. So, there’s a lot of scientific rationale in targeting this process to limit tumor growth.

Bevacizumab is an antibody that targets the ligand VEGF, and ramucirumab is an antibody that targets the actual receptor, the VEGF2 receptor. So, they have a little bit different mechanisms of action. Both work to halt the recruitment of blood vessels and VEGF signaling. I think it’s important if you’re going to use bevacizumab up front for a patient who’s treatment naïve—you’re going to use carboplatin/paclitaxel/bevacizumab or carboplatin/pemetrexed/bevacizumab—that there’s still a role for ramucirumab second-line. You haven’t burned a bridge for ramucirumab. In fact, in the REVEL data, for those patients who actually got bevacizumab first, there was still an overall survival advantage by adding ramucirumab second-line. So, if you use bevacizumab, I’ve heard a lot of second opinions say, “Well, I’ve used bevacizumab already, can I use ramucirumab second-line?” The answer is, “Yes, you can, and there is a benefit.” These drugs work a little differently, but both have shown survival advantages in specific lung cancer patient populations.

I think this is also underrepresented. At least, there’s a lack of awareness. With bevacizumab in ECOG 4599, squamous cell patients weren’t allowed. In the REVEL trial, second-line squamous patients were allowed. In this trial, ramucirumab was safe and there was a benefit in overall survival by giving ramucirumab to squamous cell patients. So, for a patient with squamous cell disease who was on chemotherapy frontline and is progressing and immunotherapy is not an option for them—and immunotherapy is an option for a lot of squamous cell patients in second-line, don’t get me wrong—docetaxel with ramucirumab is a reasonable option.

I think in the second-line, a lot of times we are trying to elicit better responses. Better responses, theoretically, can lead to better improvement in symptoms and quality of life. So, for these patients who are second-line in whom I’m thinking about trying to elicit the best response I can, I know based on the REVEL data that the addition of ramucirumab did lead to an improvement in response rates. So, certainly for a patient who’s fit, who’s symptomatic, who’s progressing on chemotherapy, who’s not an immunotherapy candidate, or who has a PD-L1 that’s very low and is rapidly progressing, or who has a specific genotype where immunotherapy would not be used, ramucirumab is a consideration.