Standard-of-care therapy in lung cancer: Be open to new ideas


This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, discussing a recent meeting of practitioners of thoracic oncology in the metropolitan New York City area. I’ll focus on some important topics related to decision-making and daily practice, and the practitioners’ thoughts from the meeting.

There’s no doubt that our outcomes are better for patients, but it’s much harder to make the best choice and I think there’s more pressure on us to make the best choice.

Topic one was the need for next-generation sequencing (NGS) testing. I’ll put it before you that every patient needs NGS testing at the time of diagnosis. It really shouldn’t be put off. How to do that is a topic for another day, but you need NGS testing.

Moving along with this, even when you’re thinking you’re going to go down the road of a checkpoint inhibitor with chemotherapy, the recent Food and Drug Administration approval for cemiplimab and chemotherapy says that you have to make sure that patients don’t have EGFR or ALK aberrations. Now, for cemiplimab, you have to make sure they don’t have ROS1 aberrations.

You need NGS testing to find those targets and give patients a targeted therapy. Even if you want to give a checkpoint inhibitor with or without chemotherapy, you need to have NGS testing.

Second, the way to get the most comprehensive analysis of targets for which there are therapeutic avenues is to do more comprehensive NGS testing, including both DNA and RNA. Not all the panels do this right now, and you really need that RNA-based testing to find all the fusions that are druggable by the current medications that we have.

Bottom line: NGS testing should be done for everybody, and you need to do the most comprehensive panel available both for DNA and RNA.

The next topic that there was great agreement on was the emergence of antibody-drug conjugates. I think everybody’s excited. All of them have shown evidence of benefit. There are varying degrees of side effects, and we’ll learn how to deal with those. They’re new drugs, they’re here, and they’re safe.

There are a couple of things to consider, though. Number one, these drugs do have chemotherapy and they have side effects from chemotherapy. I think the consensus is that when you treat patients with an antibody-drug conjugate, you need to give antiemetic regimens, at least for trastuzumab and the other deruxtecan drugs. You need to give a regimen for highly emetogenic chemotherapy as prophylactic antiemetics. I think that was a consensus thought.

Second, these drugs are making us rethink what it means to have the expression of the protein. I’m totally struck that for trastuzumab deruxtecan, patritumab deruxtecan, and datopotamab deruxtecan, the degree of protein expression is not particularly relevant, and these drugs can work in all patients. There have been cases clearly shown that datopotamab deruxtecan and patritumab deruxtecan both have benefit in patients with EGFR mutations after progression on osimertinib.

This idea of a need for overexpression, and maybe even the idea of testing, is being challenged now. These drugs seem to work as long as some protein is present. They don’t work in every patient, but they work in the vast majority. This thinking about overexpression with the antibody-drug conjugates is probably going to need to be reevaluated.

Last are some thoughts about our targeted therapies. Again, we have more targets. We have EGFR exon 20, for example, and more drugs for MET. I’d like to share a couple of thoughts on what the experts presented at the meeting.

First, although we have a bunch of new targeted agents for patients with EGFR-mutant cancers, probably the thing that’s going to change therapy now is adding chemotherapy to these agents. We may also use circulating tumor (ctDNA) to help guide us to identify which patients would be more likely to benefit from a chemotherapy with osimertinib. I see that as a trend and as a strategy that we’re likely to see move forward.

Another is in the ALK space. I know we’ve gotten very comfortable giving alectinib and brigatinib, but when you look at all the data, it points to lorlatinib perhaps being a better first-line therapy.

I think the experts thought lorlatinib would be a good drug. Yes, it has a different spectrum of side effects. The central nervous system (CNS) side effects are something we have to learn how to take care of; however, we can do that. Generally, with dose reduction, those side effects are manageable.

If you can get better outcomes in general and in patients with brain metastases, it may make some sense to displace our go-to first-line drugs, brigatinib and alectinib, with lorlatinib.

Changes in practice are happening now. There are drugs available. I urge oncologists to be open to rethinking what your standard of care is and also open to rethinking how these drugs work and to go with the data that we have.

We’re doing much better now, but the best is yet to come.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis. A version of this article first appeared on

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