Future Use of Antiangiogenic Agents in NSCLC

Corey J. Langer, MD, FACP: Angiogenesis inhibitors have clearly made their mark in advanced non—small cell lung cancer. ECOG 4599 showed a significant improvement in response rate, progression-free survival, and overall survival for the overall population—about 2 months. For the population with adenocarcinoma, it was 4 months. Maybe that’s not as impressive as some of the data we’re seeing with immunotherapy, but there’s no doubt in my mind that angiogenesis inhibitors are here to stay and that we need to perfect better ways of integrating them into the new immunotherapy paradigm. We’ve seen data for both safety and efficacy for pembrolizumab and ramucirumab in the second-line setting, and there is tremendous interest in introducing that into the frontline setting in individuals with 50% or higher expression. Trials are now under way comparing single-agent pembrolizumab to pembrolizumab in combination with ramucirumab. We’ll see similar efforts in the second and third-line settings as well—not necessarily just with bevacizumab or ramucirumab but potentially with other agents.

There are 2 studies that I would really like to see. First, I’d like to see the one that I already alluded to—combining pembrolizumab with ramucirumab in the frontline setting. I’d have total equipoise for putting my patients on that trial if they had 50% or higher PD-L1 expression. I might even opt to do that in patients with lower degrees of PD-L1 expression, based on the recent KEYNOTE-042 data. There’s another trial that I really want to see, but I’m not sure that we can afford it. Paclitaxel/carboplatin/bevacizumab in combination with atezolizumab has shown to be better than just the chemotherapy combination with immunotherapy.

I would love to go back to my pemetrexed combination—pemetrexed/carboplatin/bevacizumab plus atezolizumab or, for that matter, other immunotherapy agents. I would happily enroll my chemotherapy-naïve patients with nonsquamous cell in a trial such as that, whether it be a phase II or phase III trial. The substitution of pemetrexed for taxane reduces the risk of alopecia, neuropathy, and all the other side effects that are typically associated with taxanes. I think that becomes a much more user-friendly regimen. We’ve already seen a major survival advantage in IMpower150. I see no reason why that wouldn’t extend or go even further with a pemetrexed combination.