The Phase 3 REVEL Trial in NSCLC

Corey J. Langer, MD, FACP: The REVEL trial identified a subgroup of early, rapid progressors on frontline therapy who seemed to derive an extraordinary benefit from the combination of docetaxel and ramucirumab. Of those enrolled in the study, roughly 11% or so had progression on their frontline regimen within 9 weeks, 17% within 12 weeks, and 28% or so within 20 weeks or so. That group had a greater relative benefit with respect to survival than the overall population. The hazard ratio for the earliest progressors was 0.69. It was 0.74 for the 12-week group and, ultimately, about 0.80 for the group who had disease progression on the frontline regimen at about 20 weeks. The group included all-comers.

The overall trial showed about a 3-month difference in median survival, favoring the combination of docetaxel and ramucirumab compared with docetaxel alone. It was about 12, 12.5 months versus 9 months or so. As you’d expect, this is a more refractory group—probably worse protoplasm, worse pathology. So, the numbers are lower, but the relative benefit is more on the order of 3.5 to 4 months, or from 4 to 5 months up to about 9 months or so. So, again, this becomes a very attractive regimen for patients whose disease has progressed quickly on frontline treatment.

I’ve seen patients with rapid progression. With docetaxel alone, response rates are fairly poor—3% to 8% or maybe 10% at best. In combination with ramucirumab, those response rates more than double—18% to 20%, sometimes higher. The progression-free survival and overall survival benefit is clear-cut, so this is a group I will preferentially treat with ramucirumab and docetaxel. But I’d certainly be open to other ramucirumab combinations. I don’t think we necessarily should be wedded to docetaxel, and that’s an area that’s ripe for clinical investigation.