Targeted Therapies for Patients With Lung Cancer Exhibiting BRAF Mutations or MET Skipping Alterations

At the Great Debates and Updates in Lung Cancer Meeting in New York, New York, Rebecca Heist, MD, MPH, Massachusetts General Hospital, Boston, Massachusetts, argued for the use of targeted therapy for patients with lung cancer who exhibit BRAF mutations or MET exon 14 skipping alterations, over the use of immunotherapy.

“In lung cancer, although immunotherapy has seen tons of benefit, we are not melanoma. For patients who have BRAF V600E or MET skipping, we really should start with targeted therapy,” Dr Heist concluded.

Transcript:

Hi, my name is Rebecca Heist. I am a medical oncologist at Massachusetts General Hospital in Boston, and we're here at the Great Debates and Updates Meeting in Lung Cancer 2024.

The topic I'm talking about today is the sequencing of treatment for patients with lung cancer with BRAF mutations or MET exon 14 skipping alterations. The question is, “Should you start with targeted therapy or immunotherapy first?” I am on the side of targeted therapy, and there are a few reasons for that.

First, a lot of what we think about in terms of favoring immunotherapy first really comes from the melanoma literature. We know in DREAMseq [ECOG-ACRIN EA134], which sequenced immunotherapy first followed by targeted therapy at time of progression versus targeted therapy followed by immunotherapy at time of progression. In patients with melanoma with BRAF v600e, the sequence of doing immunotherapy first was better. That trial was stopped early because of an OS [overall survival] difference.

But lung cancer isn't melanoma, and although immunotherapy has hugely changed what we think is possible for our patients and hugely changed the prognosis for our patients, still what we see in terms of long-term survival rates in lung cancer with immunotherapy really don't approach what we see in melanoma. We can't expect that the same magnitude of benefit that we see in DREAMseq is necessarily going to be what we see in lung cancer. What we do know is that in the small case series that have been reported, immunotherapy in both BRAF v600e in lung cancer as well as MET skipping actually has relatively low response rates.

It's very possible that in these specific populations, immunotherapy does not have the same level of response and benefit that we may see in lung cancer in general. But targeted therapy, we know, has very high response rates, both for BRAF-targeted therapy as well as MET-targeted therapy and excellent median PFS [progression-free survival] and OS times. With targeted therapy, where we see these very high response rates, it is something that is meaningful for patients. When we have a response, we know people feel better, their symptoms have improved, they're eating more, their weight is stabilizing. It's something that's very meaningful and when you look at the long-term median overall survivals with targeted therapy, they really do compare well with what we're seeing in the first-line setting for IO [immunotherapy] or chemotherapy-IO in lung cancer.

To summarize, in lung cancer, although immunotherapy has seen tons of benefit, we are not melanoma. And for patients who have BRAF v600E or MET skipping, we really should start with targeted therapy.

Source:

Heist, R. Debate: Front-line c-MET or BRAF mutations: TKIs vs immunotherapy – TKIs. Presented at Great Debates & Updates in Lung Cancer; April 27-28, 2024; New York, NY.