Improving Treatment Options for Stage III NSCLC

Transcript: Laura O’Brien: Dr. Patel, I was wondering, how do you determine if a patient is eligible for surgery or if that is not an option?

Jyoti D. Patel, MD: That’s a great question. We have made tremendous gains in our surgical techniques. Often now, patients who we didn’t think could tolerate surgery before are surgical candidates because we can do minimally invasive surgery. So downtime from surgery is much less than it was. Our anesthesia has improved, and our supportive care has improved. And so every patient should ask if they’re a surgical candidate, simply because it’s a great modality for curing cancer. When people have stage III disease, the decision to do surgery becomes a little bit more nuanced because we know for stage III disease, surgery alone is never enough. So even if we can take the tumor out, we have learned—after decades of clinical trials—that patients need chemotherapy and sometimes radiation as well, depending on where their cancer is.

For people with stage III disease who have a small tumor and maybe one or two lymph nodes that are involved all on one side of the chest, surgery can be a good option. For patients who have cancer that’s on both sides of the windpipe, or what we call N3 or IIIb disease, we don’t think that surgery adds value. It can be a radical procedure, and we treat those patients with chemotherapy and radiation alone.

In patients for whom we think surgery would be a good option after some sort of systemic therapy, systemic therapy can follow two very different pathways. One can be a combination of chemotherapy and radiation. Chemotherapy makes the radiation more potent. It goes throughout your body and treats any cells that may be in your bloodstream that are micrometastatic. That usually is about five to six weeks of radiation every day with chemotherapy interspersed. And that can be tough treatment, but patients get through it, and often we can offer surgery after the completion of chemoradiation.

Another tactic for some patients is doing chemotherapy alone. So we give usually four cycles of chemotherapy, about 12 weeks of treatment or sometimes nine weeks of treatment, but somewhere in there we deliver several cycles of therapy. We give it to patients by vein. We assess them periodically to make sure that the tumor is shrinking, and after there’s been some shrinkage and control, we take patients to surgery.

The decision about who is eligible for surgery depends on a lot of patient factors, and certainly things like lung function, physical fitness and cardiovascular fitness. All of those factor in pretty heavily. We want patients to do well after surgery. By removing a lobe of your lung, you’re losing about 20% of your pulmonary function, and so you have to make sure that the other lungs are healthy. Other factors that play a role are anatomy. Sometimes if the tumor is really central, it’s difficult because it may require that we remove more than one lobe, and that could put someone at risk for being on oxygen. The other factors that we’re learning about now and trying to understand are, can we get a better handle on the biology of the disease? So are there certain patients who would benefit more from chemotherapy or an investigational approach versus chemoradiation if we thought they were marginally resectable?

Laura O’Brien: I know that when I first came to see you, you approached me about the clinical trial, and that was so scary. When you mentioned the clinical trial, I thought, “Wait a minute, does this mean there are no other options for me?” And it was after I started the investigation that I just realized clinical trials are so important.

Jyoti D. Patel, MD: Absolutely. So we’ve made tremendous gains with clinical trials in recent years. I think people come in to oncology clinics and often think that clinical trials are when patients have run out of options. In fact, clinical trials are always trying to improve the standard of care. Whatever we know, we’re building upon to make better. One huge change that’s happened recently that has led to a new standard for our patients with stage III disease is giving immunotherapy after chemoradiation. So a large trial around the world looked at patients who didn’t have resectable disease, and they were treated with chemoradiation, and afterward they were randomized. So that means the computer generated whether you got standard treatment, which was nothing following chemoradiation, or experimental treatment, which was immunotherapy for a year.

And we found a huge benefit in terms of progression-free survival—that time until the cancer comes back—but more importantly overall survival by giving immunotherapy after radiation. Within a short time after that was presented, the FDA [Food and Drug Administration] approved it, and all the guideline panels made this a level-one recommendation. And we think every patient who’s eligible for immunotherapy after chemoradiation should get it to improve survival and to improve outcomes. It’s something that was an early trial that moved from bench to bedside really quickly.

In your case, talking to you about a clinical trial, we knew that you were a candidate for resection. You had small-volume disease, you had great functional status and we wanted to get this tumor out. And really the question was should we think about chemotherapy alone, should we think about chemoradiation or should we think about participation in this trial? You thankfully elected to be in the trial, and that trial was a little farther along in development. And so I think that can also be difficult because it was a phase III trial, but it was a trial in which you were randomized to getting at least the best therapy we know of, which was chemotherapy, or chemotherapy plus immunotherapy, or immunotherapy alone. And we were comparing these three arms to see what the best outcome would be. You had a good chance of getting immunotherapy. There had been a lot of data in the past year or two really showing that immunotherapy was better than chemotherapy in patients with advanced disease. So we took those lessons that were learned, and we’re trying to bring them up to earlier stage, curable cancer to really show that benefit.

Transcript Edited for Clarity