New Paradigms for Treatment of Locally Advanced NSCLC - Episode 2

Locally Advanced NSCLC: Treatment Goals and Challenges


Mark Kris, MD: Welcome to this OncLive® NewsNetwork presentation, broadcasting live from MJH Studios. Today’s discussion will be focused on the treatment of locally advanced lung cancers and evolving treatments for these illnesses.

I am your host, Mark Kris. I’m a medical oncologist and I work at the Memorial Sloan Kettering Cancer Center in New York. Today, I am joined by 2 of my friends and colleagues: Dr. Jyoti Patel, a professor of medicine from the University of Chicago, and Dr. Walter Curran, a professor and chairman of the Department of Radiation Oncology at the Winship Cancer Institute of Emory University in Atlanta.

During the next 60 minutes, we are going to navigate through some of the questions surrounding how we treat patients with locally advanced lung cancers. We’ll discuss multidisciplinary care and consider how the availability of immunotherapies will change the treatment landscape going forward. During the last few minutes of the broadcast, we’ll answer questions related to this discussion, as submitted by the audience. We invite you to submit questions using the entry field located below this video.

What are the treatment goals for early-stage lung cancer? I think that’s a really good starting point. Jyoti, would you like to lead that discussion? What are the goals for early-stage cancer? Can you compare and contrast it to other groups of patients?

Jyoti D. Patel, MD: Sure. We still see, unfortunately, a minority of patients with non—small cell lung cancer who present with the earliest stages of disease—stage 1 and 2. Those patients are patients who have undergone lung cancer screening. Or, the cancer has been picked up because of serendipitous testing, and we find that they have a solitary pulmonary nodule. Those patients are treated with curative intent. By and large, they are treated with surgery. But, sometimes they are also treated with radiation. About one-third of patients present with locally advanced disease. Those patients have regional and mediastinal metastasis. Again, those patients are treated with curative intent. It’s a difficult process, because patients already have had some evidence of cancer beyond the lung, itself.

Mark Kris, MD: Walter, do you have anything to add to that?

Walter J. Curran Jr., MD: No, I agree with Jyoti. It’s a challenging disease. I think a lot of the lay community, and even the medical community (outside of oncology) doesn’t realize the progress that we’ve made in improving the survival of patients with locally advanced disease. This is exciting. The median survival, on the trials that we did 2 or 3 decades ago, was under a year. Most trials for good performance status patients with locally advanced disease are well in excess of 2 years, even before the trials that look at immunotherapy. So, the platform has improved. Some of it is not because we have newer therapies, but because oncologists know how to take care of these patients better. They know how to deliver concurrent chemoradiation and manage the side effects. They know how to stage patients better. The platform that we’re dealing with, regarding good performance status in patients, is much better. In those with a poorer performance status and comorbidities, the outcome is still pretty tough.

Jyoti D. Patel, MD: In addition to supportive care, where we’ve seen huge gains, there’s also some kind of migration because of better staging.

Walter J. Curran Jr., MD: Correct. There is no question about that.

Jyoti D. Patel, MD: We’re looking at a different patient population than we might have 2 decades ago.

Mark Kris, MD: One critical difference is that we do spend the majority of our time treating people with more advanced stages of the illness, for which cure is very rare. Here, cure is not very rare. The goal of therapy is cure. When you focus on cure, it changes the dynamic between risk and benefit. The best example, but an extreme example, would be a bone marrow transplant. Who would ever agree to a bone marrow transplant without knowing that there was a chance for cure? Here, we have to be really careful. We have to remember that. Obviously, nothing can be done without having a good understanding and agreement with our patients, but more risk is acceptable when there is that chance for cure. The other thing that is worth mentioning, and I’ve thought about this, is considering how many people are in this situation. The estimates say that somewhere between 40,000 and 50,000 patients are diagnosed with newly diagnosed stage 3 lung cancer. That’s a very, very huge group. To put it into perspective, all of ovarian cancers is about 25,000 cases. Here, it’s a huge number. But we have a chance to cure them.

Walter J. Curran Jr., MD: If you look at the 5-year survival data from the 1990 trials, we’re talking about a 5% to 8% rate in 5-year survival. The concurrent chemoradiation regimens are 12% to 15%. Most of the more recent trials are really in the 25% range. That’s a range not unlike what we saw with localized or limited stage small-cell lung cancer. So, we’re now dealing with other problems, in long-term survivorship of such patients, beyond the risk of recurrence of their own disease.

Mark Kris, MD: What do you think the biggest challenge is, right now, for these folks? What kind of therapy do we need, to get more into that cure group?

Jyoti D. Patel, MD: Certainly, we are making huge advances in our technology. We’re delivering better radiation therapy. The integration of our chemotherapy backbone has improved. But I would probably argue that we need to do a better job of risk stratification. We have really crude ideas about how patients may fare, based on performance status, weight loss, FEV1, or pulmonary reserve, and comorbidities prior to enrollment. But even in some of those patients, cure is possible, as you’ve said. Knowing when to push the envelope for our patients—to me, that’s the challenge, in the coming years, in understanding the biologic basis of treatment and how to allocate more precise medicine.

Mark Kris, MD: Walter?

Walter J. Curran Jr., MD: To expand even further on that point, there’s the risk of toxicity, that we have to weigh. I believe there are some patients—we don’t know how to sufficiently identify them—who are probably at a prohibitive risk for treatment-related pneumonitis, for whom you shouldn’t be pushing the radiation dose. There are other people who may benefit, based on tumor sensitivity, from pushing the radiation dose. But, we have inadequately identified them to know how to stratify them and identify them for radiation dose escalation. Those are parameters that are actively being studied. My view is, we need to study those things more.

Mark Kris, MD: To me, the greatest risk to our patients, in this situation, is not the failure of radiation. Rather, it’s the failure of the systemic therapy. We can discuss the role of radiation in controlling systemic therapy, but the vast majority of failures are not local. They’re systemic. Sometimes, they are local and systemic. But, we need a systemic therapy more than anything else.

Transcript Edited for Clarity