Rationale for Ramucirumab in NSCLC

H. Jack West, MD: Ramucirumab is a monoclonal antibody, an antiangiogenic agent, administered intravenously every 3 weeks. It is FDA approved in the United States in combination with docetaxel for previously treated patients. This is based on the REVEL phase III trial that published a few years ago, which demonstrated a significant improvement in multiple efficacy endpoints—most notably, overall survival. Ramucirumab improved that even compared with docetaxel alone, which, on its own, has a survival benefit compared with supportive care. This has been taken up by some physicians but not uniformly. I think we are likely to see a greater use of that in the future as we see a compression of chemotherapy and immunotherapy into the first-line setting, often given concurrently, which has left us with fewer options for what has active utility in these patients who have already received chemotherapy and immunotherapy.

Importantly, when we look at who was on the REVEL trial and who’s eligible for ramucirumab, this was for all histologies. Unlike bevacizumab, this did allow for patients with squamous and nonsquamous non—small cell lung cancer. The REVEL trial actually demonstrated that the benefit seen with that combination was even seen in the subset of patients who had received prior bevacizumab. There were no safety signals that precluded patients, based on histology or other factors, from safely receiving the docetaxel/ramucirumab combination. Even the patients who had received prior bevacizumab could benefit, so it certainly is an option for patients. I use it in my own clinic and I have seen good tolerability and efficacy with it. I am more inclined to use it for patients who have a good performance status, who are being delivered into the second-line setting after progressing.

It’s important to bear in mind that we sometimes have patients who have received several lines of treatment, including those who have received a targeted therapy for a driver mutation. They may have gotten 1 or 2 lines of treatment for a driver mutation, and chemotherapy and immunotherapy. But as long as patients have a performance status and bone marrow function that’s suitable for treatment with docetaxel, you can add ramucirumab to that. It really adds very little in the way of toxicity risk. With that, you get to confer a greater overall survival benefit. I would be inclined to use it in the second-line setting, but you should also be aware that it has been studied in the third-line setting, and is very feasible for patients as long as they haven’t received prior docetaxel and have the performance status and bone marrow function.

I’ve used the combination of docetaxel and ramucirumab in many of my patients in the clinic increasingly over the last several months to years. The biggest toxicity issue I run into is hematologic. There’s a greater tendency to need growth factor support. Patients develop neutropenia, occasionally with fevers. Just by being very vigilant about monitoring their counts, mid-cycle, and being aggressive about initiating growth factor support when needed—that’s really all that’s been necessary. The nice thing about using the combination is that it hasn’t really led to a change in practice. I’ve just needed to ensure that patients’ counts are followed carefully, and that when you need to introduce growth factor support, you do so.