Researchers Look to Refine Use of Radiation in Oligometastatic Lung Cancer

Kevin Stephans, MD

There are several questions surrounding how radiation therapy—especially combined with other agents—fits into the treatment paradigm of patients with oligometastatic lung cancer, according to Kevin Stephans, MD.

“As we get more phase III data, we will have a better understanding of where it fits,” explains Stephans, who discussed oligometastases during the 2016 OncLive State of the Science Summit on Metastatic Non—Small Cell Lung Cancer. “Does it fit in upfront, or does it fit in later? Do we treat patients upfront when they have the biggest burden of disease to get rid of resistant clones, or do we go with simple treatment upfront and hold it for the time of progression?”

In an interview with OncLive during the meeting, Stephans, associate staff, Radiation Oncology at Cleveland Clinic, recaps the latest research in oligometastases for patients with lung cancer.

OncLive: What is new in the space of oligometastatic lung cancer?

Stephans: Most patients who have metastatic disease will present with multiple metastatic sites all over the body—though a small percentage will present with more isolated disease. Obviously, most of the therapies—such as the systemic chemotherapy or immune chemotherapy—are going to address disease anywhere. Stereotactic body radiation therapy is a particular technology that could address only localized disease.

The advantage is that the side effects tend to be few because the treatment is localized, and the disadvantage is that it is only going to address disease at that site. There are different prognostic ways to pick patients who may be likely to progress at 1 or a few sites only. People who are younger with fewer sites are more likely to have a long response to chemotherapy. As long as those sites are not located somewhere that would be too toxic to deliver radiation, they could safely be treated. A very small set of patients may benefit from that therapy.

What do community oncologists not know about this type of disease?

We do not have randomized trials that look at randomizing “yes or no” to radiation. We have trials that suggest that patients who are radiated do well, but we do not really know what the benefit of radiation is because they may just be people who were well-selected who were going to receive that treatment anyway. It is important to be very careful in choosing which patients receive which treatments. If they strictly meet the criteria, and they are expected to tolerate therapy, then that is a good way to go.

Another thing that has surprised people in the past is that, when radiation is combined with some different systemic agents, that regimen is also well tolerated, though occasionally there are expected side effects.

Using radiation together with a VEGF­­-targeted agent, such as bevacizumab (Avastin), has associated toxicities that are much higher than what was expected. That is one thing to be really careful of in these patients who are doing well; they are probably going to get more therapy down the line because they are still going to be a good fit. We have to be careful on how we select those therapies and be aware that they have had radiation in the past.

Are there any ongoing clinical trials for these patients taking place?

Most of the clinical trials have been phase II studies, so all of the patients receive the intervention. At the 2016 ASCO Annual Meeting, there were finally some phase III studies coming out in which people were randomized to consolidate a radiation, or consolidate a local therapy versus a more systemic therapy. It is too early to have data on survival, but the progression-free survival was pretty long. It was over 1 year for the radiated patients, and it was longer than it was for the patients on additional systemic therapy—for those with 1 to 3 sites and stable disease on their prior chemotherapy regimen.

It is a reasonable option for those patients; it allows the oncologist to hold back effective systemic therapy a little bit longer, and then have an agent available in the future.

What are the biggest questions surrounding patients with oligometastases?

Again, one of the biggest questions concerns is where this type of therapy fits in, and people often discuss cost-effectiveness, as well. All of that may change as agents are out for longer periods of time. It is a moving target, and it is the same thing with radiation. However, one advantage is that radiation is a one-time therapy, or it does not have to be continued and repaid-for every month, so it may be very cost-effective in that model. Again, that is a moving target.