HER2- and MET-Mutation/Amplification Therapies

Video

Transcript:

Mark A. Socinski, MD: We want to talk about a number of oncogenic drivers. Thomas, at the American Society of Clinical Oncology [ASCO] 2017 Annual Meeting, you presented some data regarding HER2 amplification. Make the distinction between amplification and mutation, and discuss the data.

Thomas E. Stinchcombe, MD: Something that has been difficult with HER2 lung cancer is how to define it: by immunohistochemistry [IHC], amplification, or mutation? Robert Lee, MD, at Memorial Sloan Kettering Cancer Center did a trial with HER2 mutations. He found that it was T-DM1, which is approved for metastatic breast cancer. He had an overall response rate [ORR] of 45%, as well as a good progression-free survival [PFS] of 5 to 6 months. This is a single center and a small trial, with 18 patients. It’s actually in the National Cancer Comprehensive Network [NCCN] guidelines. It is an option.

We also did a trial that used IHC to define it. There were no responses in the IC2-positive stage. In the IC3-positive cohort, there were 4 responses out of 20 patients. There are some challenges because the patients with HER2 amplification and mutation are different. We need to refine the biomarker for this; it is a potential marker, however, for further drug development.

Mark A. Socinski, MD: So probably not a first-line option but certainly a subsequent line at some point in that population.

Thomas E. Stinchcombe, MD: Yes. We’ve all had some patients who’ve gotten chemotherapy, and there are limited options. I wouldn’t use it up front in anyone at this point, but I think it’s something to consider when you’re running out of options.

Mark A. Socinski, MD: There is also the issue of transitioning to broad testing from a molecular standpoint, looking at a number of different targets because, you know, if you’re in that 40% group that has a robust response, that’s pretty meaningful to that particular patient.

Thomas E. Stinchcombe, MD: This drug is well tolerated; it’s really meaningful to that patient.

Mark A. Socinski, MD: We have high MET amplification and the MET—exon 14 skip mutation. There was some enthusiasm a couple of years ago regarding crizotinib; we saw data at the World Conference on Lung Cancer [WCLC] with crizotinib and tepotinib. Your thoughts in that setting?

Leora Horn, MD, MSc, FRCPC: Crizotinib was the first data we saw that showed it was a MET inhibitor. There is more activity in the MET—exon 14 skipping mutation, in my opinion, than what you see in patients with MET amplification. The tepotinib data we saw at WCLC were actually in patients who were EGFR-mutation positive looking at the idea that MET is a mechanism of resistance that can be combined with gefitinib [Iressa] and tepotinib.

There are also nice data looking at tepotinib as a single agent in patients with MET—exon 14 skipping mutations and MET amplification. Tepotinib seems to be more potent than crizotinib, and perhaps better tolerated. That may become an option in the future. There are several other drugs for that space too.

Mark A. Socinski, MD: Yes.

Maximilian Hochmair, MD: I am a coauthor of the tepotinib study. This drug is certainly well tolerated for patients with MET amplification. It doesn’t last long, but in the mutated population it has longer periods of potency. Tepotinib and crizotinib as well last 3 to 6 months.

Mark A. Socinski, MD: It also depends on how amplified you are. In the highly amplified cohort, it has more activity than if you’re borderline in that setting. D Ross Camidge, MD, presented some data regarding the patient population with lung cancer mutation, which showed that low levels of amplification are not active.

Leora Horn, MD, MSc, FRCPC: Yes, they must be 3-plus or higher.

Mark A. Socinski, MD: Or even 5-plus or higher.

Transcript Edited for Clarity

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