Part 4: Whether to Switch Treatments After Discovery of MET Mutations in NSCLC

News
Article

During a live virtual event, Martin Dietrich, MD, PhD, discusses how to address switching treatments in response to detection of a MET gene biomarker.

Martin Dietrich, MD, PhD

Martin Dietrich, MD, PhD (Moderator)

DISCUSSION QUESTIONS

  • What factors would influence your decision to use or not use a MET inhibitor in the first line for an eligible patient? What factors would influence which agent you recommend/select?
  • What if a patient had a MET amplification instead of a MET exon 14 skipping mutation?

MARTIN DIETRICH, MD, PHD: What are your thoughts on using the medication in the first-line setting over chemoimmunotherapy? We don’t know exactly how chemoimmunotherapy works [in this setting], since nobody has studied this specifically; but the biology would predict it to be less efficacious, similar like we do with EGFR inhibitors.

Are there any factors that would influence your decision-making, such as adherence or brain metastases? If you see a patient that has started on chemoimmunotherapy, how would you switch? Is there a little bit of a practice-share? How do you choose between capmatinib [Tabrecta] and tepotinib [Tepmetko]?

LUIS RAEZ, MD: I think either drug is OK. I have treated more people with capmatinib because it came first. But I am also interested in using tepotinib, and I think we really use 1 of the 2 instead of crizotinib [Xalkori] because we have plenty of evidence that crizotinib doesn’t protect the brain very well. That’s why I think we should go for capmatinib or tepotinib. I would advocate that you restart the chemoimmunotherapy because you didn’t get the NGS [next-generation sequencing] on time. I think we should stop it and give the patients a chance with the target therapy, as we do with other targets, and then don’t wait until they fail the chemoimmunotherapy to consider the target therapy.

OLEG GLIGICH, MD: I agree, you can go back and forth between the 2. But convenience is huge, because with tepotinib it’s only 2 pills, whereas with capmatinib it’s 4. If patients aren’t going to be tolerating multiple pills, that’s one way.

The other thing to take a look at is MET amplification. With MET exon 14 skipping, you would probably feel more comfortable just using tepotinib. But I think for MET amplifications, you could either use capmatinib for both amplifications and exon 14 skipping mutations; I wanted to know what everybody else’s thoughts on that approach are.

HARSH AMIN, MD: I just want to add one thing about capmatinib and tepotinib. Capmatinib is [available as] a sample, so it’s easily available. I think the company’s doing a good job. If I have a patient, if a sample is ready to go, that influences a little bit in decision-making. Otherwise, like I said earlier, there’s no head-to-head comparison that first-line capmatinib does look better than tepotinib, if you look at the numerical value of overall response rates, so that’s another reason I use capmatinib. When there is a sample, so the label is available to go, that’s another factor that plays a role. I think both drugs have the same brain response rate, so I don’t think that will make a difference.

DIETRICH: It’s a good problem to have, to have 2 very efficacious drugs in this setting. I think convenience is probably the biggest differentiator.

AMIN: I believe MET amplification response rate is much lower, and so I think the chemoimmunotherapy is probably better, at least in the first line. Maybe in the second line, the drug can be used. But that’s as MET amplification is a different situation than MET exon 14 skipping.

DIETRICH: For the MET amplifications, the level of amplifications is something that is really important.

AMIN: Correct, more than 10 [patients], I believe, had a higher response, about 30%.1 Maybe in that situation, it can be used.

DISCUSSION QUESTIONS

  • What if a MET exon 14 skipping mutation was found after front-line chemotherapy or chemoimmunotherapy had been started?
  • Would you switch therapy or wait to progression?
  • In cases of progression on first-line chemotherapy or chemoimmunotherapy, what regimen would you be most likely to choose for a patient with a MET exon 14 skipping mutation?

DIETRICH: In the post-osimertinib [Tagrisso] EGFR setting, we see the MET amplifications as a major resistance factor. I typically try to not [switch treatments] by getting a liquid biopsy first, but when I make a first step, I typically treat until the patient progresses, and I don’t really switch arbitrarily. I try to avoid it if I can.

KOCH: I would tend to agree with that. These patients are incurable, so the goal is quality of life, and maybe extension of life. If a patient is tolerating whatever therapy they’re on, and they are either responding or stable, I tend to stick with that mode of therapy before I entertain switching to anything else.

DIMITRIOS AGALIOTIS, MD: In the positive cases for the MET exon 14 skipping, what kind of histology would the patients have? Say, in non–small cell lung cancer, was their histology adenocarcinoma, squamous, or non-squamous?

DIETRICH: It goes 2 ways for the MET exon 14 skipping. It’s most often found in adenocarcinomas. It’s somewhere between 1% and 5% [of them]. If it is a sarcomatoid histology, I think the percentage is over 50%. If you have a sarcomatoid differentiation in the lung, the MET exon 14 skipping is probably the highest probability. I don’t think there are much data in squamous or other histologies.

I do want to say that, now that KRAS [inhibition] is approved, and so many other investigational markers are coming, I would sequence all non–small cell lung cancer histologies—squamous, large-cell, and adenocarcinomas. We still have most data in the adenocarcinomas, but it is no longer a big issue in getting it approved. Sometimes the histology assignment is wrong, and sometimes we get surprised by what we find based on the genetics. While the probability is higher, I think the chance for finding them in all other parts here is important.

REFERENCE

1. Paik PK, Felip E, Veillon R, et al. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020;383(10):931-943. doi:10.1056/NEJMoa2004407

Related Videos
The Oncology Brothers with Joshua K. Sabari, MD, presenting slides
The Oncology Brothers with Joshua K. Sabari, MD, presenting slides
The Oncology Brothers with Joshua K. Sabari, MD, presenting slides
The Oncology Brothers with Joshua K. Sabari, MD, presenting slides
The Oncology Brothers with Joshua K. Sabari, MD, presenting slides
Related Content