Targeting MET Exon 14 Skipping Mutations in NSCLC

Part 3: Factors in Using MET Inhibitors and When to Switch Inhibitors in NSCLC

During a live virtual event, Ravi Salgia, MD, PhD, discussed how to decide whether to use a MET inhibitor in the first line and whether to switch to a MET inhibitor from other treatments.

DISCUSSION QUESTION:

  • ​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?​ Are brain metastases a factor?
  • What if a MET exon 14 skipping mutation was found after frontline 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?

RAVI SALGIA, MD, PHD: Would you switch therapy or wait for progression? Would you do it if chemoimmunotherapy had been started? Those are all important questions. What about brain metastases?

SWARNA CHANDURI, MD: I did the initial MRIs, but my patient is so far negative for brain metastases.

SHERRY HSU, MD: Yes, I would agree to do the initial MRI of the brain. Some small molecule inhibitors do have brain activity; I’m not sure about the data on the MET inhibitor.

If it’s a small, stable, asymptomatic brain metastasis, I do feel comfortable using the targeted therapy to treat first.

VEENA CHARU, MD: I have a question for second-line treatment. If a patient is on capmatinib [Tabrecta], and they’re PD-L1 positive, would you add immunotherapy?

SALGIA: I would not add immunotherapy in combination with capmatinib. I think that’s a dangerous combination.

CHARU: Then, as a second line, you’d go for chemotherapy?

SALGIA: Yes, that’s a little bit controversial. I tend not to add immunotherapy, I just go with chemotherapy, because I think the majority of these tumors are “cold” tumors. Are they going to be responsive to the immunotherapy, or are you just giving them a drug and it’s the chemotherapy that’s doing the activity? So, I tend not to do immunotherapy as much as possible. Every once in a while, I have done it and I have been disappointed. At least from the literature, and from our clinical experience, we tend to do chemotherapy.

In terms of any thoughts about convenience, either one is OK, capmatinib or tepotinib [Tepmetko]. Dr Charu, are you OK with that?

CHARU: I’m OK with that, but I think usually taking 1-a-day dose is much easier for patients rather than taking twice a day.

CHANDURI: On the contrary, if it is twice a day, maybe dose reduction will be easier by skipping 1 dose or lowering the dose.

SALGIA: Either one is OK. I have a patient with a MET exon 14 skipping mutation, an older gentleman who has a lot of comorbidities. I had put him on tepotinib at 450 mg. He’s had generalized anasarca, so I held [treatment] and he’s much better now. So, I’m going to dose reduce from 450 mg to 225 mg. What’s nice is I just told him, instead of taking 2 [pills], just take 1. That made it easy for us. So, that’s another factor. It depends on your patient’s compliance, depends on your comfort of using these kinds of drugs.

MERIN STEPHEN, MD: Is there a preference between the 2 drugs, if they have a brain metastasis?

SALGIA: No, no preference. Capmatinib has activity against brain metastases; and…we published that tepotinib has brain activity, as well. So, either one is just fine.

DISCUSSION QUESTION

  • What if a patient had a MET amplification instead of a MET exon 14 skipping mutation?

CHARU: If patient had MET amplification, since you know the responses are slightly lower, would you prefer to use first-line chemotherapy, or do you still go for MET inhibitors?

SALGIA: If it’s an older patient, with a lot of comorbidities, I use it as first-line; but, if it’s a more robust patient with not too many comorbidities, I go for the chemotherapy first. You’re exactly right. Ideally, if we can get them on a clinical trial, that is the best way to go.