James Stevenson, MD
Although immunotherapies, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), have generated great excitement in the field of squamous non–small cell lung cancer (NSCLC), a number of targeted agents are also gaining recognition, according to James Stevenson, MD.
The monoclonal antibodies necitumumab (Portrazza) and ramucirumab (Cyramza) are both approved by the FDA to treat patients with squamous NSCLC, and researchers are further examining the agents to determine their optimal use.
During the 2016 OncLive
State of the Science Summit on Metastatic Non–Small Cell Lung Cancer, Stevenson, a medical oncologist at Cleveland Clinic, discussed developments and ongoing research in squamous NSCLC.OncLive: What are your thoughts on where the field of squamous NSCLC is currently? Stevenson
: Advanced squamous NSCLC sort of trails behind some of the other subtypes of NSCLC, in terms of new treatment approaches—especially targeted therapies where we really have not had some of the breakthroughs that we have had with other lung cancers. Not to say it is completely bleak, but there have been several trials that have looked at targeted agents such as monoclonal antibodies to the epidermal growth factor receptor (EGFR) or antiangiogenic agents targeted to VEGF that, unfortunately, have not proven to be that effective in squamous cell cancers.
There is a drug called necitumumab that has recently been studied. It is a newer generation EGFR monoclonal antibody that does look like it has some upside—especially in squamous cell cancer. That is a drug of interest, especially in EGFR-overexpressing tumors, so that has been a recent breakthrough in the treatment of these patients.
Another exciting aspect in the treatment of squamous cell cancers is the Lung-MAP trial (SWOG S1400)—or the Master Protocol—which is a multi-institutional trial that is being led by the National Cancer Institute. We are actually looking at different targeted therapies to treat squamous cell cancers in the second-line setting, where they are tested for actionable targets in 3 different pathways.
If they have alterations in those targets, essentially looking at PI3 kinase, CDK 4/6, or FGFR, then patients can go into targeted therapies in those treatment arms. There is no placebo arm in those trials, which is great. The trial has been altered in that way.
It is also a very inclusive trial. For patients who do not have any of these biomarkers on their genomic testing, they can be treated as part of Lung-MAP and will receive either a combination of nivolumab and ipilimumab or nivolumab alone. It is an all-inclusive trial for squamous cell patients in the second-line setting that we think is one of the best clinical trial options for these patients right now, in terms of new approaches.What are the most important takeaways for community oncologists in this space right now?
There are other agents that we can incorporate into the treatment of squamous cell cancers, including some agents that have been recently approved and can be given in combination with chemotherapy. Their clinical benefit is potentially better in certain subsets of these patients. It is up to the oncologist to decide, based on using these drugs, whether they think the benefit is there—especially when we talk about cost and quality of life for these patients.
Regarding necitumumab and ramucirumab, these are new agents that are available for oncologists to use for advanced squamous NSCLC in the frontline and second-line settings. They are expensive agents, and they do have toxicities associated with them. The benefit with the addition of those drugs was not as eye opening as some of the immunotherapy results have been, so that is why the uptake in practice has not been as robust as immunotherapy.
We are definitely thinking about how to use these drugs and hoping that we can find biomarkers to use them in a more intelligent fashion.
How do you see this landscape evolving over the next couple of years?
We will have a completely different paradigm in the use of immunotherapy in the frontline setting for many of these patients, so many of our patients with squamous NSCLC will not get chemotherapy as their first treatment; they will get immunotherapy. Therefore, using chemotherapy potentially with some of these other agents, such as necitumumab, will be pushed back a bit. It is not going to go away, but it might. Chemotherapy may be the new second-line treatment 1 year from now.
We are going to have to use it more wisely because performance status may not be quite the same in the second-line setting. It is going to be a different situation than we are used to when using chemotherapy—especially platinum doublet agents. In 1, 2, and 3 years from now, it will be even more different, so it will be a good challenge to have. Again, data are going to be what we need to help decide on these treatments, as well as our own clinical experience and cost.