Treatment options for patients with lung cancer are rapidly improving, leading to better and more durable outcomes. Since 2018, the FDA has approved 21 different drugs or drug combinations for the treatment of various forms of lung cancer, with 6 of those approvals coming in May 2020 alone.1
With the resounding success of osimertinib (Tagrisso) that was recently presented in trial results at the 2020 American Society of Clinical Oncology (ASCO) Virtual Program, and several in-progress clinical trials exploring therapeutics for molecular targets and early-stage disease, the treatment paradigm for patients with lung cancer is poised to change.
ONCOLOGY® recently sat down with Mark G. Kris, MD, of Memorial Sloan Kettering Cancer Center to discuss the recent trends in lung cancer treatment and the avalanche of therapeutic agents moving through the development pipeline that have already begun to redefine the accepted standards of care.
Q: What are the major trends in lung cancer right now?
Kris: Well, I think an overarching thing is that in lung cancer treatment today, there really isn’t a patient who gets managed by just 1 specialist. Whether or not other modalities are added, [the course of treatment] is very patient-specific. There needs to be a discussion [for every patient] about the role for other treatments. For example, radiation in metastatic lung cancer, after some benefit from a systemic therapy, is something that’s done routinely now, and something that would never have been done years ago. In fact, if you did radiation, you’d be outed as somebody who was practicing way outside the [standard of] care. But that’s now a standard thing. And I think there are good reasons for that, biological and practical as well. So, I think that’s among the biggest things—that we now need to consider everything that could be done.
In a case presented at last year’s [New York Lung Cancers Symposium] a small tumor in a patient was discovered, and the tumor could be removed surgically, it could be treated with radiation, or intervention radiologists using a bladed procedure could also do it. So how do you choose among these options, particularly for that individual patient? And that’s a challenge. It really is. This is the discussion that goes on in an institution—when you say, I’m going to operate on this person, the radiation oncologist says, well, wait a minute, have you considered this? Or the intervention radiologist says that, too, and how do you take all those opinions and choose what the right treatment is?
And now, after you have a curative surgery, who gets additional systemic treatments? I think this year the presentation at virtual ASCO [on results from the phase 3 ADAURA trial], about giving osimertinib to patients with resected lung cancers, is going to change things, because normally many of those patients would not have been considered for therapy, or if they were considered for chemotherapy, would be considered too complicated of a patient. But this is now an option that most patients could have. So, every patient needs to have this consideration of treatment.
Another issue is the need to consider every patient for testing now. It was not a standard of care to do mutation testing on every patient who had a resected lung cancer. It is now. So how are we going to do that? And why are we going to do that? So, these are the kind of things that are important right now, taking advantage of breakthroughs and putting them into practice.
Q: Can you talk a little more about the importance of genomic testing for lung cancer?
Kris: There are characteristics of every tumor that define the course of the illness. Understanding those characteristics—and it might be a mutation, it might be amplification, but it also might be what kind of T cells are in that person’s tumor—can point you to a therapy. I think EGFR is a very good example. It’s very specific. If you have this EGFR mutation, the tumor cells are very sensitive. It’s also a diagnostic test for lung cancer. No other cancer has these EGFR mutations. If you have it, you’ve got lung cancer. There are a lot of implications of that. But [having a] better biologic understanding gives you a better chance to match a treatment to the cancer in that person. And we all want to do that. That’s something we’ve all struggled to do, instead of giving treatment ‘X’ to everybody. We’re doing that again now with checkpoint inhibitors. Everybody gets a checkpoint at some point in their care, unless they have a target. But I think that’s the biggest thing about the mutation testing: It helps you define a patient, it helps you define the tumor in a patient and lets you match the treatment. And we’re trying to carry that paradigm forward as much as we can.
Q:What are some of the other major changes you’ve seen over the course of your career?
Kris: When I began in this area, there was no treatment for metastatic lung cancer. So, if you were 53 years old and you had lung cancer that spread to your liver, you were sent to the phase 1 clinic, because there was no treatment. And if you were going to go on a National Cancer Institute trial, any drug that they had would be given to you as the first treatment. Any drug. Whether it had any relevance to lung cancer or not, that was the standard of care.
Now, we have a lot of treatments that are specific to lung cancer that really changed the face of the illness. Previously, there was an unmet need; people didn’t focus on it. And I could agree with those people because there wasn’t yet a clear path forward. A lot of the tough cancers have that characteristic, because there isn’t a clear path forward. The investigators and young doctors entering research groups say, “Well, why are you going [into lung cancer]? Stick with leukemia, we’ve made some progress, and if we understood it better, we’d make even more.”
Whereas with lung cancer, there was no progress other than operating. So where are you going to start? That kind of was the issue with me. I was very lucky because I was allied here with our surgeons. Our surgeons were experts and they knew everything about the illness. They knew everything about surgery, including where the problems were—like those cases where they did successful surgery, but the patient didn’t survive anyway because the cancer grew back. And it was the surgical leadership, actually, that dragged all of us into trying to do adjuvant and new adjuvant treatments to patients, because they saw that people, despite a successful surgery, had metastasis at some point and they look for systemic therapies. But that was very helpful to me, too, because we had that the surgical base here, and they really focused in on the problem: the people who weren’t cured by an operation. They gave us the chance to help cure those people.
Q: To you, what’s the most exciting work going on right now in your field?
Kris: Well, the bottom line is to cure [the patients]. So, things that have a chance to cure people with advanced lung cancers are, to me, the most exciting, and one of those things would be the use of immunotherapeutics.
When you look at the clinical trial results for people who got immunotherapeutic agents, you see that in some patients with stage IV cancers, the cancer doesn’t come back. We all have these patients in our practice, and it’s pretty unusual for patients with metastatic cancer for the cancer just not to come back. Their life goes back to normal. It’s pretty amazing, and it’s kind of interesting that, [if you read the] medical literature, nobody wants to say they’re cured. It’s the same in other cancers, too, like the melanoma space. People don’t want to say these people are cured 5 years later after having metastatic melanoma, and no cancers have come back. Every disease site is controlled, but people don’t want to say they’re cured.
Q: Which trials or treatments are making the biggest impact or poised to make the biggest impact in the lung cancer space right now?
Kris: I think the data Roy Herbst presented [from the phase 3 ADAURA trial] at the virtual ASCO meeting [represent] a game-changer. Going forward, large clinical trials, that are completed already, studied giving postoperative checkpoint inhibitors, T cells, and preoperative checkpoint inhibitors in an attempt to improve outcomes with surgeries or surgery and chemotherapy. We’re waiting for the results. So, that’s the next very hopeful group of trials that [could] change therapy. The other big completed trial was of durvalumab (Imfinzi) after concurrent chemotherapy and radiation. We went for decades without improving upon giving chemotherapy and radiation for people with locally advanced, but not steady, cancer—people who were not able to have surgery. We tried all kinds of things; nothing helped. In fact, some things harmed. And then suddenly, by giving a year of durvalumab, more people are cancer free afterward and more people are cured there, too. So, I think that’s the other really important trial of the last 5 years.
And we continue to chip away, with new drugs for the various mutations: MET, HER2, BRAF. Drugs for all of these are getting approved. Capmatinib (Tabrecta) for MET exon 14, entrectinib (Rozlytrek) for ROS1, these drugs…they chip away at [the cancer] but they’re not yet part of a curative package. They shrink the cancer and they shrink it well for a period of time, but it doesn’t lead to a cure. But trying to parlay that information to a cure is our challenge.
Q:How is coronavirus disease 2019 (COVID-19) affecting care? How has it changed your practice?
Kris: Well, an addition [to the New York Lung Cancers Symposium] this year will be a session on practice and tele-oncology: how to look for ways to provide care and do it in a way that is appropriate right now with COVID-19. I think the message is, you can’t—and we’d like to think we didn’t—you can’t stop the delivery of care for patients with lung cancers, for any reason. It can’t be stopped. So our challenge is, How do we continue to provide the same level of care, and the same complexity, with the right decision making, when there’s this unbelievable force pervading everything and making it very, very hard to continue care? That was the issue for us. It wasn’t taking care ofCOVID-19. It was continuing care in the face of COVID-19. So, for our patients, with all the different issues that they face, none of them went away. And COVID-19 was added to that list. So, that’s the problem, both for us as doctors, and for our patients and their families.
The other thing is, and this was an unintended consequence, we tell people put your care team together, have the people that are important to you be at the visit, be your second set of ears, be there to ask the questions that you might forget. And now that’s gone. That person isn’t there. They’re banned from the building. So, they’re physically isolated, and then they’re humanly isolated by the people that they have chosen to rely on, to help them make these decisions. So, that’s been a real hardship for patients.ν
Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
1. FDA approvals in lung cancer treatment. Lung Cancer Research Foundation. Updated June 2020. Accessed July 21, 2020. https://www.lungcancerresearchfoundation.org/research/why-research/treatment-advances/
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