Considerations for Antiangiogenic Therapy in NSCLC

Benjamin P. Levy, MD: In KEYNOTE-189, patients were allowed to go on to maintenance pemetrexed/pembrolizumab. The question really is, if we’re instituting these 3 drugs—carboplatin, pemetrexed, and pembrolizumab—what do we do next, when patients either can’t tolerate the regimen, experience side effects, or have progression? This is really an area that we’re still trying to learn. The data has come out so rapidly and unexpectedly, showing the survival advantage. We’re trying to learn what to do next. In my mind, what to do next is often a clinical trial. That’s important. We need answers for patients in this setting. They’ve already gotten immunotherapy upfront. As a maintenance strategy, immunotherapy is probably not the best next option.

One of the drugs that could be considered is docetaxel. It’s been a tried-and-true drug. If you’re going to consider using docetaxel in a patient who has either progressed on triplet therapy or can’t tolerate it, you should also consider adding ramucirumab. This was obviously borne out of the REVEL trial, which looked at docetaxel versus docetaxel plus ramucirumab. The addition of ramucirumab provided a meaningful benefit in response rate, progression-free survival, and overall survival.

We need to do more work in this space—post carboplatin, pemetrexed, pembrolizumab. But certainly, in my mind, if I’m going to give a patient docetaxel, if they are a candidate, I would consider adding ramucirumab.

Ramucirumab has a place in relapsed-refractory non—small cell lung cancer. This, of course, is evidenced by the REVEL trial. This was a trial that looked at a large number of patients who had adenocarcinoma or squamous cell carcinoma, who had progressed on platinum chemotherapy. Some of these patients also had used bevacizumab in the platinum regimen. They were randomized to either docetaxel or docetaxel plus ramucirumab. The bottom line, in a very clean study, was that the addition of ramucirumab in these patients improved response rate, progression-free survival, and overall survival.

I think this regimen is becoming more important as we think about new frontline regimens. The changes that we will see in frontline regimens with the triplet therapy of carboplatin, pemetrexed, and pembrolizumab highlight and underscore the importance of this combination as a second-line combination strategy.

The addition of ramucirumab did not increase toxicities very much. Certainly, there were some increased toxicities, but they weren’t prohibitive. I think the REVEL trial was practice-changing. It offers another opportunity to deliver antiangiogenic drugs in combination with docetaxel for patients who progress on a platinum regimen.