Second-Line Metastatic NSCLC: Treatment Landscape and Challenges

Rebecca Suk Heist, MD, MPH: Yes. Our standard first-line therapy for patients with non-small cell lung cancer who don’t have any actionable drivers is either immunotherapy or a combination of chemotherapy and immunotherapy. The question is, what are the standard second-line options for these patients? Focusing on the patients with non-small cell lung cancer who don’t have actionable genomic alterations, in the second-line setting we are really looking at single agent chemotherapies. In the United States, docetaxel is approved in this setting and in the second-line setting it has shown responses that range around the 10% range. There are data from the REVEL study of using docetaxel with ramucirumab [Cyramza]. Ramucirumab is an antibody against VEGFR [vascular endothelial growth factor receptor]. In the REVEL study, patients were randomly assigned to receive either docetaxel with ramucirumab or docetaxel with placebo. That study showed improvements in both progression-free survival [PFS] and overall survival [OS] with the addition of ramucirumab. Docetaxel with ramucirumab is another option in the second-line setting of patients with non-small cell lung cancer. We think about the second-line setting as a place where there is actually a lot of room for possible improvements because whether it’s docetaxel alone, docetaxel with ramucirumab or any of a number of other single-agent chemotherapies, they do have some response base. They do have some improvements in PFS and OS. Overall, the results that we see for patients is not as good as we would hope and there’s a huge unmet need in that setting to have new and improved therapies.

Why is it so important to enroll patients in clinical trials in this setting? What we know from the data of the standard therapies out there is that we can get some responses and prolongations in PFS and OS with the available chemotherapies. For example, the addition of ramucirumab to docetaxel. At the same time, the benefit that we’re seeing isn’t as much as we would want for our patients. Clinical trials are a way to try new experimental drugs that have good scientific rationale to see if we can improve the outcomes in this setting. All of us would say that the recent advances in the first-line treatment of non-small cell lung cancer have made great inroads in how people are doing, and people are definitely living longer and better with their cancers. At the same time, we know that most of the time people will progress, and we need better therapies for patients in this setting. The only way to get better therapies from what we have now is to try and test new ideas in the clinical trial setting. Enrolling in a clinical trial is really critically important to advance how people do with lung cancer and how people live longer.

Solange Peters, MD, PhD: The most important and severe unmet need in the field of normal adeno non-small cell lung cancer today is to know what would be the best second or even third line of treatment. When you think about these patients receiving combination of chemotherapy and immunotherapy frontline. When you come to the second line, it looks like it’s a real bottle neck. There’s nothing else you can offer apart from the classical. Remember, the docetaxel second line was published in 2000. We don’t like docetaxel, it’s difficult to administer, it has many side effects. We also know that the activity of docetaxel is limited.It’s very rare in oncology, but the unmet need is about defining subsequent lines of treatment from the second line on. Which means potential substantial improvements in overall survival.

It’s important to enroll patients in clinical trials envisioning, analyzing, or evaluating second-line or third-line treatment because, first, we have this unmet need. We don’t know what to give instead of docetaxel. More than that, it’s not so easy to enroll patients. By definition of clinical trials, a patient needs to be fit and have this difficult resilience to go into clinical trials already in second line after failure of chemotherapy and immunotherapy. Meaning that these patients who are willing to support this clinical research are precious and international collaboration can be the only way to move a path forward. As I mentioned before, the data comes from 2000 telling you how difficult it is to establish new standards in this specific second-line slot in our fragile patient population. Few patients are strongly selected but they exist on a daily practice, and we need to work together to create new evidence.

This transcript has been edited for clarity.