Top Takeaways in Lung Cancer From ASCO 2022

The American Society of Clinical Oncology (ASCO) annual meeting is the stage for presenting many of the most impactful advancements in cancer research — including in lung cancer.

In this second of four exclusive episodes, MedPage Today 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 reviewing the most influential lung cancer research presented during the meeting and providing insights on how the new data will influence clinical practice.

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.

Jorge, you first — what do you consider the most impactful study you’ve seen here at ASCO?

Nieva: Well, I think I’m gonna disappoint you, Roy, because it’s not a lung cancer study. I thought the most impactful study was Dr. [Shanu] Modi’s presentation of the DESTINY-01 data in breast cancer. And what was really impactful about that study, I think, is that it showed us that for the last 20 years, everything we thought about a particular biomarker might have been wrong.

And I think the oncology community is a very empiricist community. We like to see the data and prove your science. And I think it was absolutely wonderful and very brave and daring to go out there and say, yeah, this cutoff that we’ve been using for HER2 for the last 20 years, maybe we need to change that cutoff and really benefit our patients. And so it was just so exciting to see the HER2-low population benefiting.

And I think we can learn a little bit as we’re developing lung cancer drugs about that as well, where we start thinking about, what’s gonna be the right way to use these antibody drug conjugates [ADCs] for patients who have low expression of EGFR. So I think it’s going to really open up a lot of possibilities for benefiting our patients.

Herbst: I’ll agree with you, but I’ll also contest that it’s not only a breast cancer study, because we can now move this to other tumor types. And, I recall from my days at MD Anderson years ago doing immunostaining and we actually published that there is HER2 staining in lung cancer; you can pick it up. So we could perhaps start to use these targets in lung cancer patients.

Nieva: Absolutely.

Herbst: So I think that, yeah, it was quite a packed room there. And clearly these ADCs are something for us to watch in lung cancer, especially as we’re trying to boot up to the next immunotherapy combinations, antibody drug conjugates. We take an antibody, with a linker, with a toxin — really could have some great effect.

So Sarah, you’ve gotta have a lung cancer study.

Goldberg: Of course I have a lung cancer study, though I agree that was an amazing study and a great presentation. So I think in the lung cancer space, there’s a lot of areas that we need to make improvements in, but I think one of the most frustrating areas has been after immune therapy failure. How do we try to overcome resistance to immune therapy? And so, I’m not just saying this because I know you’re closely involved in this study, but I was really excited about the Lung-MAP study.

So, looking at pembrolizumab and ramucirumab in the second line after immune therapy failures, there’s an overall survival benefit there compared to standard chemotherapy. So that’s huge. I mean, I think we really haven’t seen that. There’s been so many trials, so many combinations trying to show a benefit of some combination, some immunotherapy combination after relapse on prior immunotherapy. And I think this looks really exciting.

And so, I think it probably needs some more work to confirm if this is something we should be doing in standard practice, but I was excited to see that trial.

Herbst: So this is the abstract by Karen Reckamp …

Goldberg: Exactly. Yes.

Herbst: … that was actually published simultaneously in the Journal of Clinical Oncology. And yes, seeing a positive study. And one thing that’s nice about that study in a lung master protocol is it was open at 600 to 700 sites around the country. So providing access, right?

Goldberg: Exactly. So not only was it a positive study in and of itself, which is a great advance, I think the fact that it was a lung MAP study — I think that’s an incredible resource for patients and access to trials and throughout the country, it reaches so many different people and academic centers, community centers.

And so — of course you’re very closely involved in it — but I think having a trial where you try to match patients to a biomarker, and then if there’s no clear match on the trial going into this unmatched arm, that’s an amazing framework for a trial and to see a positive study come out of that is really exciting.

Herbst: Right, and I guess for my two cents, certainly there are a number of incremental advances we saw with new targets against EGFR exon 20, EGFR resistance, KRAS come in to play. You presented some data showing KRAS mutations and drugs working with some activity in the brain.

But I’ll say the thing that was most impactful to me in lung cancer was Everett Vokes’ Presidential Symposium. And the fact that there’s such a focus now on access, and getting drugs to the patient at the point of care, and he spoke about that. What good are all these targeted therapies in immunotherapies? Then we heard from someone from the WHO, the World Health Organization, talking about ways that we can bring drugs and profiling and therapies throughout the country.

So I think that was a big theme of this meeting — innovation, but also access and bringing the newest therapies forward. So I’ll use that as my contribution right now.

Let’s say if you were to take a number two — Do you have a number two, Jorge, that might work in lung cancer?

Nieva: Well, I really like the FDA pooled analysis of patients with PD-L1 over 50%, asking the question whether or not you need to add chemotherapy to that group. And it was great to see the FDA asking a scientific question that only they could uniquely ask. And so pooling the results of all the different trials and really showing that for patients who have PD-L1 over 50%, you don’t have to give them chemo.

The overall survival is going to be very similar, whether you do it or not. And a suggestion that for patients who are over the age of 75, really you want to be very cautious about using chemotherapy in that group. I thought that presentation was really impactful, at least for my practice.

Herbst: Great. So the big data really analyzing things and learning from aggregate experiences, collaborative work.

Nieva: Yeah. And it’s wonderful. And I think it was something that the FDA was uniquely poised to be able to do. And so I’m so glad they did it.

Herbst: And Sarah, you have a number two?

Goldberg: I mean, maybe collectively, but I think we’re starting to see some more signals of drugs in, as you mentioned before, in the EGFR space. So overcoming EGFR, first-line EGFR TKI resistance, I think we’re starting to see some drugs maybe that are combinations that might have activity.

We saw a really nice presentation about amivantamab and lazertinib. I think that looks promising. It’s not gonna be the answer for all patients, but I think that might be something we might have in the future for patients.

Some new exon 20 drugs, EGFR exon 20 drugs that look promising as well. So I think that whole space, we have had great advances there, but I think now we’re seeing the next generation of drugs and some drugs in exon 20 space with less toxicity potentially that I’m excited about.

Herbst: Okay. And I’ll just give you as probably the oldest person at this table. This is my 27th ASCO. Now, two of them, of course, by video. But when I first came to ASCO Los Angeles, carboplatin paclitaxel was the big story. Everyone was excited that we had chemotherapy that was giving us a 20, 25% response rate in an advanced disease and a 1-year survival of 30%. And that was an improvement. Maybe 20 to 30%.

So I think we’ve come a long way. And the one thing that I tell people, I just came from the posters is, yeah, these are incremental, making slow progress, but we’re on the shoulders of all the progress that has been made. And now we’re in a much more personalized world where we’re understanding the biology of cancers and using those biomarkers. So it’s good. I always leave Chicago really excited — and also tired and wanting to go home. Right? Okay.

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