2016 ASCO Annual Meeting Research Round Up – Lung Cancer, with Jyoti D. Patel, MD

September 22, 2016
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In today’s podcast, Cancer.Net Associate Editor Dr. Jyoti Patel discusses some of the new research on lung cancer presented at the 2016 ASCO Annual Meeting.



ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology known as ASCO, the world's leading professional organization for doctors that care for people with cancer.

In today's podcast, Cancer.Net associate editor Dr. Jyoti Patel, discuses some of the new research on lung cancer, presented at the 2016 ASCO annual meeting. Dr. Patel is professor of medicine and the director of thoracic oncology at the University of Chicago. The ASCO annual meeting is the premiere educational and scientific event where physicians, researchers, and other health care professionals, gather to discuss the latest in cancer care and treatment. This Cancer.Net podcast helps put new research findings into context, and explains what they mean for patients. ASCO would like to thank Dr. Patel for summarizing this research.

Dr. Patel: Hello, My name's Jyoti Patel. I'm professor of medicine at the University of Chicago and director of the thoracic oncology program. I am thrilled to give you some updates about ASCO Annual Meeting 2016, in lung cancer, because certainly there were, I think, some advancements that are important for physicians and patients and caregivers to know about. So first, the broad categories I'm going to talk about are targeted therapies, immunotherapy, progress in small cell lung cancer, some questions about radiation, and then finally, a web-based application for patients.

So first let me start with targeted therapy, because certainly that has been one of the consistent themes over the past ten years, ever since the advent of drugs that block EGFR, tyrosine kinase. I think at this meeting we learned again that there is broad agreement that the 15% of patients who have EGFR-mutant lung cancer at diagnosis, have great options for initial therapy. There are three good drugs that are on the market, gefitinib, erlotinib, and afatinib, and all of them have durable responses. I think that areas that were perhaps more interesting and I think will really impact patient care in the near future, is how we can follow patients with liquid biopsies. We know that most patients who have frontline therapy will eventually have progression on these drugs, and there are questions about whether we can test tumor DNA that's been isolated from the blood and whether that is as good as a standard biopsy to figure out why patients develop resistance. And that's important because we now have drugs that treat resistance.

The drug osimertinib has good activity in patients who have a particular new mutation called the T790 mutation. What we learned from data presented from clinical trials that the drug rociletinib was in fact liquid biopsies are pretty good. They are not 100% effective, but in 70 to 80% of folks who have progression, a liquid biopsy or simple blood draw may serve just as well as a tissue biopsy, and it may be a first step. Certainly, our technology is changing very quickly. Five or six years ago, this seemed like a dream we wouldn't get to or wouldn't be a reality any time soon, but it is in a clinic near you, in fact. The FDA has approved the Cobas EGFR mutation test, which is a blood-based test, very recently.

The other targeted class of agents that I'd like to talk about are for patients with ALK translocated lung cancers. So, A-L-K, or ALK translocated lung cancers occur in about 4-5% of patients, and they represent a distinct group of patients who should receive targeted therapy in the frontline setting, similar to EGFR patients. So these patients generally, in 2016, are treated with crizotinib as a frontline drug. We know that most patients again experience disease progression on crizotinib, and that average is at about a year. We have two drugs that are approved in the second line setting, alectinib and ceritinib, in the United States.

So one of the important trials, and one that I think could be practice-changing very soon, is a trial called J-Alex. It was a Japanese study to see whether or not we could move that second line drug, alectinib, to the frontline setting. About 200 patients either got crizotinib or alectinib. And what we found that patients who got the alectinib, the approved second-line drug first, had a progression-free survival or that time until the cancer worsened that was over twice as long as crizotinib, moreover, it was better tolerated, and this is important certainly. This is in a Japanese population. There is a larger international study that's being conducted. But this may mean that we can move this second drug into the frontline setting, and importantly for patients, the drug alectinib has penetration into the brain, so it can prevent or treat brain metastasis.

There's another new drug for patients with ALK translocated lung cancer called brigatinib, and that, too, is an oral drug, and it looked to have nice responses in patients who've had prior crizotinib with over 70% of patients having disease shrinkage. Finally, there was a fair bit of discussion about other targeted agents for RET and BRAF, and I think the story continues to evolve that we are finding more and more mutations that we can target, we're getting front and second-line drugs, and we're understanding mechanisms of resistance, and these are coming to fruition faster than we had ever imagined.

The next area and to me I think the biggest winner in ASCO that I'd like to discuss is small cell lung cancer. So small cell lung cancer affects about 15% of patients with lung cancer, and unfortunately, we have made few strides in the treatment of small cell over the past three decades. The chemotherapy has been the same. We've made some advancements in radiation for a patient but, unfortunately, this has been a very difficult disease. But there were two really important things that will, I think, change our approach to this disease. One is the advent of a targeted drug for patients with small cell. So the clinical trial that was presented by Charlie Rudin looked at a drug called Rova-T. And Rova-T targets a protein that's produced by small cells, and that protein is delta-like ligand three, or DLL3.

Rova-T is a drug-antibody conjugate. So it essentially locks onto DLL3, which is present on small cell lung cancers, and then releases its payload which is a toxic drug which kills small cell. Importantly, up to 70% of small cell lung cancer patients have DLL3 on their cancer cells. And in patients with the highest levels, we saw up to 60% response rate. So this is very exciting. Importantly, the toxicity profile was modest, so patients did pretty well. Sometimes they developed some fluid. But certainly, this is an early study. A phase three study is under way. But this is something we're very excited for. This looks to be better than our current second and third line options.

Also, there was great progress in understanding that immunotherapy may be a good treatment option for patients with small cell. So in a study that was presented by Dr. Scott Antonio, a PD-L1 blocker called nivolumab was used alone or in combination with a CTLA-4 drug called ipilimumab, and in this trial patients who had had prior treatment for their small cell and had what we considered sort of refractory and tough to treat disease had some important responses. So about 10% of people responded to the single drug, about 20% of people responded to both drugs. But what was most exciting is that some of these responses were very durable. The responses were ongoing at over six months. The toxicity profile of both of these drugs was also encouraging and it was well tolerated. They were few treatment discontinuations for most patients.

Building on that theme, immunotherapy continues to evolve for patients with lung cancer. So we know that we have two FPA approved drugs nivolumab and pembrolizumab. But questions have been surrounding which patients might receive these in the frontline setting. Can we combine these drugs with other checkpoint inhibitors? Can we combine them with chemotherapy? And some of those early answers are coming through. There was a study called CheckMate 012 which looked at frontline therapy with nivolumab plus ipilimumab. And patients who highest levels of PD-L1 expression, the response rate and the frontline setting so before chemotherapy was significant, it was over 70%. This is a very small study and we await some of the other frontline studies but certainly we're beginning to understand whether or not we can deliver these drugs to patients, perhaps upfront, or in combination with chemotherapy to improve outcomes.

A couple of things that I think are important to mention, certainly, in radiation, I think have implications for practice, and patients might want to talk to their physicians about this. One was based on an abstract that Dan Gomez from MD Anderson presented, and this was looking at radiation for patients with stage IV disease. We know that patients with good initial response and good disease control from frontline chemotherapy, are most likely to eventually have progression, or growth of their tumor in the residual sights of disease. And this trial which was primarily at MD Anderson - a few patients were treated at other sites - but this trial randomized patients who had gotten initial systemic therapy, and had less than three sights of disease, to either standard therapy - which in many instances, was more chemotherapy, and some was taking a break from chemotherapy, and starting an observation - versus radiating those leftover sights of disease or those areas that were still active. And in that trial, it seemed that the time until the cancer grew was four times as long in patients who had radiation or local control for their disease.

Now, I think this is a preliminary study, and certainly there is a national trial by NRG that's being planned to validate these results, but I think the question is, how do we really personalize therapy? If someone has a great response to systemic therapy, and has maybe one or two sites of disease, is there a way that we can add different treatment modalities to improve outcomes? And certainly, to sort of get to the heart of that question in how we can best tailor therapies for patients, another study that I think was important was comparing proton therapy with standard therapy. Now, there has been great interest in the community, and certainly with my patients, in bringing proton therapy to standard therapy for patients with lung cancer, and the idea is that proton therapy is energy is delivered to the tumor itself, and there's not much drop-off. The energy goes just to the tumor, and we feel that perhaps we can have less damage to other important organs, maybe less damage to her heart, or the surrounding lung.

The study really didn't find that [chuckles]. In the study, we found that there was really not such a difference in outcome, and certainly there are ongoing trials that are further investigating this, but I think all of us that reviewed the data feel that most patients are best served by conventional therapy. There are different risks for patients receiving proton therapy - certainly, there's problems with expertise and delivering it and access, but it doesn't appear to change outcome.

Finally, one of the abstracts that I was most excited about was a trial that came from France. And this study looked at a web-based application in which patients were able to report their symptoms every week. This was a personalized web app that 130 patients were enrolled. And either they had standard follow-up, their regular doctor visits, and regular imaging with CT scans as standard of care at least every three months, or this web-based application where they would have the same doctors' visits, but instead report their symptoms every week. And the reporting of their symptoms could trigger an email alert to a physician. So the top line result is number one, that survival in patients was much higher, seven months higher, in patients on the web application than in patients who received standard care.

I think this has multiple implications. So one, the patients probably know their symptoms the best, and can let us know when we need to intervene. I think the second important part of this was this was not cumbersome for most physicians. It took about 15 minutes to manage on a weekly basis, to manage their email alerts and decide what to do. Certainly this decreased unnecessary CT scans, it improved communication between a team and their patient. But to me this is the best personalized therapy we can give for patients. A seven month improval in survival would certainly get a drug approved. This kind of web-based application and personalization of therapy I think would be important. And we are eager to see whether we can do this in other countries. Certainly there was great interest generated in this and with technology moving as quickly as it can, it may be that we would see this with broad application in the near future.

Certainly I think this ASCO Annual Meeting was a great one for lung cancer. A lot has changed in recent years. We think about the advent of understanding oncogenes and how to target them with EGFR inhibitors approved just over a decade ago. Now to having multiple driver mutations that we can target. Adding immunotherapy, particularly for patients who don't have these targeted therapies. And I think this next year we'll understand whether or not immunotherapy in the frontline setting makes sense and how to integrate immunotherapy with other modalities. Questions about sequencing with chemotherapy adding to radiation. Those questions will likely be answered in the next couple of years.

And then finally I think this idea of true personalization for cancer care. Certainly we have deadlines and we know on average patients have progressive disease, but really trying to personalize it. We understand that survival is a broad-based bell curve for patients with lung cancer. And so understanding patients that may need more interventions more frequently versus those patients who may be doing quite well with disease control and those who we can personalize therapy and follow-up so they can continue to have very full lives. So thank you very much. I hope that this has helped with putting some of these lung cancer advancements in perspective. Thank you.

ASCO: Thank you Dr. Patel. To learn more about the science presented at the 2016 ASCO annual meeting, visit www.cancer.net/ASCOannualmeeting. If you have questions about whether new research may affect your care, be sure to talk with your doctor.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients world-wide, and supporting initiatives to ensure that all people have access to high-quality cancer care. Thank you for listening to this Cancer.Net podcast.