Halmos Zeroes in on Year Ahead for Lung Cancer Treatment

Balazs Halmos, MD

The year 2021 will encompass a bigger focus on neoadjuvant and adjuvant trials, more novel molecular compounds for more select subgroups, and a migration of circulating tumor DNA (ctDNA) into a more minimal residual disease (MRD)–based setting, according to Balazs Halmos, MD.

“2020, despite being a terrible year as a result of COVID-19, actually has been a good year for thoracic oncology,” said Halmos, a professor of medicine at Albert Einstein College of Medicine and director of the Thoracic Head and Neck Program at Montefiore Medical Center. “As for next year, I think it will be hard to replicate what we've seen this year in terms of the great successes, but there are definitely a number of stories that will continue to unfold.”

In an interview with OncLive, Halmos reflected on the most exciting advances of the past year in thoracic oncology, and also gave his predictions for what will unfold in 2021 as it relates to lung cancer treatment.

OncLive: Let's look at the big picture for lung cancer for next year. What are some trends that you see on the horizon for 2021?

Halmos: [First in looking at 2020,] kudos to all of the companies for completing their studies, kudos to the clinical investigators for putting patients on studies, and kudos to the patients for participating. But, certainly, the FDA has done a fantastic job in the middle of this pandemic in taking their job very seriously and looking at data quickly, so that patients can receive medications that are more effective, but also safer. [It also includes] oral drugs, [lower-grade] safety profiles, and not necessitating visits to the physician. They are often also changing the schedules of some of the immunotherapies that we're offering to our patients to a more convenient schedule. The FDA has done a great job this year.

One that is the highlight now for 2021, but certainly is in very early stages, is the KRAS story. We will learn a lot more in the coming year or 2 as to what the activity of the different compounds is. How can they be combined with conventional treatments up front, with chemotherapy, or immunotherapy, or [will it be used] as second-line treatment? Is there some benefit of 1 compound versus the other or are there particular molecular combinations—for example, with the KRAS G12C [inhibitor]. There are some of the downstream inhibitors—for example, the SOX inhibiting compounds—so there is great excitement in that field. That's a significant subset of patients, so it will be very important to watch.

Another aspect is looking at the smaller, but still very important, molecular subsets. We've seen a lot of exciting data about EGFR exon 20 insertion–positive patients. Those data sets will continue to mature and the FDA might make some calls on some of the leading molecules. We do anticipate some great excitement there. ERBB2 is emerging as a real target now in lung cancer with these excellent antibody-drug conjugates that have shown success in breast, colon, and gastric cancers, and likely will yield great benefits in ERBB2–positive lung cancer patients, as well.

Of course, ERBB2 is a complex target in lung cancer; we have ERRB2 mutations, and different types of ERBB2amplification as well. There's a lot that we need to learn as to which particular patient subsets could be the best candidates for these novel approaches.

Of course, with immunotherapy, we will continue to find new ways to benefit our patients. The TIGIT molecule had brought a lot of excitement. But, there are definitely a lot of other approaches as well that we’re so keen to support. That could include different vaccines that are being developed that can include expanding different lymphocyte subsets now. It can also be a more individualized approach; it's almost like the CAR T-cell therapy approaches that are being investigated in some of these particular subsets. There is a lot of excitement there.

Let's not forget that, ultimately, we want to cure more patients, so bringing all of this to an earlier-stage setting where we have the highest chance for cure will be so important. Some of the adjuvant studies with immunotherapy compounds will start reading out and will be incredibly important to watch out for and quickly integrate if positive results are obtained. We are keeping our fingers crossed for that. And, of course, we are incorporating these novel compounds, especially the immunotherapy combinations into the stage III setting. In PACIFIC, we've seen a major advance, but why not take another step forward? We do want to support those studies as well. We'll be very eager to see the readout of those.

You already highlighted a handful of new molecules. Are there larger, phase 3 studies for next year that you're anticipating?

Definitely the adjuvant studies [are anticipated]. Some of them might have readouts, and some of them completed accrual maybe about 1 year ago. They will take some time to mature, but maybe some inkling will come out. Especially, if the results are very positive, you may get an earlier read vs if the results seem to be fairly similar between the experimental and control groups.

Another one that I'm very eager to see is a compound called canakinumab. This is kind of an anti-inflammatory agent that actually came from left field from the cardiovascular literature, where they found that as much as it did benefit patients post-myocardial infarction to some extent, but it also did reduce lung cancer incidence by almost 50% in those studies—stunning results in a way. There are a number of phase 3 clinical trials that are being completed and are likely to read out very soon. It will be very good to see that because that will be a completely new class of compounds that could impact our practice. I'm very curious about that.

What were the biggest advances in 2020 as it relates to molecular testing?

It's hard not to think about molecular testing, with the ease that we have now with ctDNA as something that you have to continue to bring up. Each practitioner needs to start being familiar with the platforms that can be used so conveniently, so easily, and so powerfully to impact patient care, and now we have very validated settings in lung cancer. We are very ahead of all other fields.

We know that up front, if you have limited amount of tissue, it may be not enough to complete testing. Or, if there's a need to speed up testing, due to a very symptomatic, sick patient, etc., ctDNA can make a huge impact. If you identify an actionable alteration by ctDNA, you can act upon it as if it was detected in tissue. It also is very important in the acquired resistance setting to monitor secondary changes; that can impact second-line and subsequent lines of therapy.

I'm very eager to see now ctDNA moving into kind of the MRD platforms, where we can maybe detect MRD after surgery or definitive chemoradiation and maybe we can use it to monitor immunotherapy responses. We've seen a lot of exciting technologies this year reflecting that, so that's the next wave—the MRD detection with the ctDNA platforms that are being developed, for example, by Signatera. There is also great excitement about early detection as well, with some of these novel technologies.