乌鸦传媒

New clinical research unveiled at the recent has the potential to significantly alter the treatment of lung cancer. But what will be the innovations we are talking about in 5 years? Or 10 years?

In this last of four exclusive episodes, 乌鸦传媒 brought together three leaders in the field -- moderator Roy S. Herbst, MD, PhD, of Yale Cancer Center in New Haven, Connecticut, is joined by Jorge Nieva, MD, of the Keck School of Medicine of USC in Los Angeles, and Sarah Goldberg, MD, also of Yale Cancer Center -- for a roundtable discussion on how to get to the next level in lung cancer, and what they and other experts will hopefully be talking about at ASCO over the next decade.

Following is a transcript of their remarks:

Herbst: Welcome to our roundtable on lung cancer here in Chicago at ASCO 2022. I'm Dr. Roy Herbst from the Yale Cancer Center. I'm also joined by my colleague, Dr. Sarah Goldberg from the Yale Cancer Center, and Dr. Jorge Nieva from the University of Southern California.

Well, it's been great talking. I have one last question, which is really on my mind. How are we going to make further progress? And I personally think it's going to be bringing science to bear on disease. We've already talked about this in a neoadjuvant and adjuvant setting, bringing small molecules and immunotherapy to bear, but Sarah -- liquid biopsies are very much in my mind and minimal residual disease. Do you think we can use those and how will those become something that could be used to tell us who needs more therapy in the metastatic or the adjuvant setting?

Goldberg: So I think just in general, this idea of biomarkers is so important. I'm so glad you brought it up. I think a couple of things before I answer your question. I'm going to just make a general comment about biomarkers.

I think you could really think about things two ways. I think in a lot of ways we want to be inclusive and not narrow the eligibility for trials to a specific biomarker too soon. We saw that in the breast cancer studies you were talking about. Because you don't want to miss patients that might benefit from a treatment. But I think when we've seen the most benefit and the most progress it's been in biomarker-selected patients in the targeted therapy realm.

So I think understanding the biomarkers and understanding the science and what's happening at the molecular level is so critical.

And so as all this, these trials, move forward and we get data and we have understanding of what's happening in patients, I think we really have to bring that back into the lab and try to understand what's happening in the tumor, and then trying to find the biomarkers that predict for that benefit. That's going to be so important. And then designing the next round of trials to try to fine-tune the patients as much as possible without omitting patients that still might benefit.

But to answer your question about liquid biopsies, I think now liquid biopsies in so many people's practice, in lung cancer specifically, has become so much a part of standard of care. We're doing that all the time now. And when we first meet a new patient with a new diagnosis with metastatic disease, getting a liquid biopsy to characterize the tumor and understand the molecular drivers -- so that's become part of the standard treatment.

And then I think now the next maybe two pieces that are going to hopefully be brought in is, can we use liquid biopsies or ct [circulating tumor] DNA or other blood-based biomarkers to track responses and think about maybe switching early or adding on early for an inadequate response that you might not capture by imaging, but you might capture by ctDNA or other blood-based biomarker?

So those types of studies are now really starting to begin. And they're hopefully something that we will see in the future, where we can fine-tune our treatment of advanced disease based on blood-based markers.

And then for the minimal residual disease question, I think that's also going to be key. We're starting to see that in colorectal cancer, where we could potentially select patients based on a blood biomarker for adjuvant therapy.

I don't think we're there yet for lung cancer, but there's a lot of work going on in that space. And so I hope that one day we can do that. Because we're now seeing all these great options for neoadjuvant therapy, adjuvant therapy, adjuvant targeted therapy, adjuvant immune therapy. And how do we know which ones to use? Does everyone need chemo? Does everyone need immune therapy?

It would be really nice to know when we can hold back on treatment and not give someone too much toxicity, but also when does someone really need all of the above and they really need to have elimination of all the micrometastatic disease that might exist. So I think that's going be so important.

Herbst: I couldn't agree more. And maybe you can say a few words, at the Yale Cancer Center you're involved with the Lung SPORE [Specialized Program of Research Excellence] grant that's taking translational work from the lab to the clinic. How do you work with a basic scientist? I know you work with a couple of very basic scientists -- you being a more translational scientist, how do you work together to solve problems?

Goldberg: Yeah, so we have this grant, which I think ... we've had amazing science I think all along and basic translational and clinical, but the really nice thing about a grant like this is that it helps to bring us all together even more and really interact and talk to each other about what we're seeing in our respective fields.

So, the basic scientists are discovering things in the lab and they're bringing it to us more clinically oriented people, saying, what does this mean? Is this useful? Is this something we can take forward in patients and bring to a trial quickly?

And so we've seen that. We've seen discoveries in the lab, I think at a pretty, pretty quick pace being brought into the clinic and looked at in patients. And then of course the reverse, right? We see something interesting in the clinic, an unusual mechanism of resistance or an unusually profound response or something unique, and then bring that into the clinic to try to understand it better. So I think it just brings all the people that are doing great work together and in a remarkable way to do even more. So it's a really fun way to work.

Herbst: So teamwork to really attack all this and personalize lung cancer.

So I know you're doing very similar things, Jorge, at USC. Thoughts on how we're going to use the latest in science? Maybe taking from other disease areas and really go to the next level in lung cancer?

Nieva: Well, I think we're going to need to use things that all scientists have developed, but we're really going to need better preclinical models. I mean, right now we have about 1,300 drugs in development and that's a wonderful blessing that we have, but we only have about 40,000 patients enrolling into clinical trials in the United States.

So it's not enough patients to test all the drugs we have. And it's a big problem that we need to actually solve I think scientifically.

We need to have better models, better preclinical models, that predict whether or not something's going to work. And I think at this meeting we've all seen the disappointing news around TIGIT as a potential therapy for lung cancer ...

Goldberg: Small cell.

Nieva: ... for small cell lung cancer. At this meeting.

So I think we're going to need to have better ways of knowing what is going to work and what isn't going to work. Because our precious clinical trial patients are a limited resource, and we're going to have to find ways of making more happen with the resources that we have.

Herbst: Right, I agree. Well, okay. Let's go into a lightning round now. So what I'm going to do is I'm going to ask each of you two questions I'll give it to you in advance. One is going to be ASCO in 5 years -- what will be the main story in lung cancer? And then maybe ASCO in 10 years, where we're going. So, in no particular order, Jorge -- 5 years?

Nieva: Five years: we're going to know exactly when patients are cured and when they're not cured, and when they need additional therapy.

Herbst: Okay. Sarah?

Goldberg: I'm trying to to decide if this is 5 years or 10 years, but I'll just say hopefully 5 years. I think we're going to hopefully be able to personalize immune therapy a little bit better. I think right now everyone is getting a PD-1 or a PD-L1 inhibitor. And I hope that with better immune profiling, understanding the immune microenvironment, we'll be able to give combinations to people based on certain characteristics in their tumor.

We're not there yet, but I hope that we will be able to do that. Because as you said, there are so many drugs. And so to be able to personalize it is going to be really important. Will that be 5 years? Might be close.

Herbst: Okay, now I'm going to go 10 years -- Jorge?

Nieva: We're going to be in 10 years, I think we're going to be personalizing not just the tumor, but we're going to be personalizing treatment to the patient.

We've become very good in oncology about learning everything we can about the tumor, but the host, the patient that's living with the tumor, we need to know more about how their genetics, how their environment, how their physiology, is going to impact their response to the cancer therapy.

So I think we're going to move from an area where we personalize based on tumor to personalize based on the whole person.

Herbst: Okay, good. Sarah?

Goldberg: Oh my goodness. You know, I think we are going to have to start to think about better trial designs so that we can find the right drugs quicker. And so that it's not this massive enterprise that takes years and a lot of money, so then the drugs are insanely expensive because I don't know how all this is sustainable with all of these drugs and trials and all.

So I think there maybe needs to be better ways to do trials so that hopefully by 10 years, we will be able to more quickly and more efficiently find the answers to what is effective and then have treatments that get to patients faster, and are more possible to get to all patients because of the finances and in other countries and people have access everywhere to them.

Herbst: Okay. And I have one final bonus question. I'll answer this one too. Are we curing lung cancer or will we in the future, Jorge?

Nieva: I think we're curing lung cancer now. There's about 350,000 people alive today who wouldn't have been alive 10 years ago if we didn't have all the advances that we have. So I definitely think there's a number of patients that we're curing. And I think we're just going to get better.

Goldberg: We've been curing early stage lung cancer and locally advanced lung cancer, but in too small a subset of patients. And I think now we're curing more of these early stage locally advanced patients.

I think the real question is, are we curing patients with metastatic disease? And I think we are now finally starting to do that. We haven't talked about this at all, but I think our definition of oligometastatic disease has expanded. And I think that's going to lead to more cures for patients because we're using local therapies on more patients with metastatic disease. And then hopefully as our immune therapies improve and we get them to more patients, we're going to be curing patients with immune therapy as well. I think that probably will be a small subset of patients that are cured with systemic therapies, unless those drugs get better and are more fine-tuned. But I think we are.

Herbst: Right, I agree. Always in the early disease, but not enough. We need to find more of that with better screening. Maybe more primary prevention as well. But clearly in the metastatic setting, immune therapy does cure some patients in my opinion. It just doesn't work for all.

So that's where everything we've talked about comes together. We know we can cure some patients, but we need to bring science to bear to figure out what's happening with the other 80 or so percent who are not, or 85, that are not having those amazing responses to immunotherapy. And I think that's something we'll be talking about here in Chicago for years to come.

Well, I thank you both for your time. It's great to spend this hour with you and I hope you enjoy the rest of the meeting and hopefully we'll talk again next year.

Nieva: Always a pleasure to speak with you, Roy.

Herbst: Thanks Sarah.

Goldberg: Thanks.

Watch episode one in this series: Neoadjuvant Chemo Plus Immunotherapy in Resectable NSCLC

Watch episode two in this series: Top Takeaways in Lung Cancer From ASCO 2022

Watch episode three in this series: Unmet Needs in Lung Cancer

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