Roy S. Herbst, MD, PhD: The REVEL trial compared docetaxel, a standard second-line lung cancer therapy, with docetaxel plus ramucirumab, the VEGFR2 antibody, and included both squamous and nonsquamous lung cancer. Actually, the toxicity results suggest that one could give the drug in both settings, and there was an improvement in survival across the board in both the squamous and nonsquamous settings. Off the top of my head, the hazard ratio was in the mid-0.8 range—not the highest ratio one has ever seen, but clinically and statistically significant.
There is some benefit. This drug was approved almost at the same time as nivolumab. Many people are, in the second-line setting, using nivolumab, which has relegated this regimen to the third-line setting, but I think that it is clearly better than docetaxel if one were going to use docetaxel, adding minimal additional side effects. I also believe that ramucirumab might have some role in immunotherapy in altering the microenvironment—in favor of the immune therapies working better.
Toxicities are managed in the usual ways. When you add ramucirumab to docetaxel, the main toxicity is still going to be neutropenia—probably only slightly exacerbated by the VEGF inhibitor—and certainly neuropathy. You would manage it with supportive care; treatment of febrile neutropenia, when that develops; and blood product repletion, if that’s needed. We’ve gotten pretty good at giving docetaxel. It’s a tough drug, but certainly very manageable.
In the second-line setting these days, most people would use immunotherapy unless they really have a reason not to. The reasons not to would be some sort of autoimmune disease, pneumonitis, psoriasis, something preexisting that would make you concerned about using an immune checkpoint inhibitor that would activate the immune system, or someone who is terribly symptomatic to the point where you are worried that the immunotherapy wouldn’t happen for more than 2 or 3 weeks before the patient needs something to be done for their symptoms. There, you would want the best
response you could get, and that would probably be with a docetaxel and ramucirumab combination.