Anaplastic lymphoma kinase

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The following presentation from Answers in CME is part of an educational activity titled Sustaining Long-Term Care with ALK-TKIs in Metastatic Non-Small Cell Lung Cancer, Best Practices for Adverse Event Management.

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This activity is supported by an educational grant from Pfizer International, LLC.

I work with a lung medical oncologist, and I'm also an adjunct professor at the UBC School of Nursing.

We're going to be talking about the best practices for recognizing, monitoring, and managing adverse events associated with L-conhibitors.

So when we think of the ALK alteration, is it common? Not really.

It's only in three to seven percent of all the non-small cells we see.

So when you think about the molecular classification of sarcomas, might be a way to look at it is like you have these simple karyotypes, right? You have like the kit mutations, or sometimes you might have Ntrek fusion driven sarcomas.

We have ALK alterations also in IMD, another type of sarcoma.

So there's those simple karyotype that you can identify and even fusions, I think I've put under there.

So translocation associated sarcomas tend to be simple karyotype.

And as we see Protax and other things come up, I think there is a potential that these will become targetable in the future.

That's the hope, of course.

But today, in 2026, what fusions or alterations that we have targeted therapies? You mentioned the N-TRAC, you mentioned the ALK, which obviously there are many therapies that target them.

But how often is sarcoma driven by N-TRAC or by ALK?

For all non-squamous, and you can consider for squamous, the panel should cover at least 80%.

EGFR, KRAS, ALK, ROS1, BRAF, NTRK, MET Exon 14, RET, HER2 mutations, NRG1 plus HER2 IHC, and CMET HGF receptor IHC along with the PD-L1.

EGFR, ALK, RET, PD-L1 carry Category 1 designations, and that list continues on.

CMET-IHC and HER2-IHC are now part of routine workup because there are drugs tied to these.

And one caveat, plasma circulating tumor DNA is a complementary tool, especially when tissue is scarce or if you need the speed of that, but it does not replace tissue.

Subsequent-line options are single-agent amivantinib or sunvocertinib.

Note, movocertinib was withdrawn from the market after the Phase 3 Exclaim 2 trial failed.

And so next, what about the treatment of ALK rearrangements?

But what really gets exciting is when you are able to put a patient on trial where you're using a therapy you can't get any other way, and particularly if it looks super impressive.

As an example, I wanted to just take a look back at what's happened with ALK.

where we're going from, you know, about 15 years ago, starting out with crizotinib and landing now with lorlatinib, first-line metastatic setting, more than seven, eight years, PFS, electinib in the adjuvant setting.

Josh, the same, I should say, the same applied to TDXD in 2021.

And then they report it with a hazard rate of 0.17. Any thoughts about where we are right now in terms of KRAS G12C, Solange?

Well, it's quite interesting, and I think we discussed it in the past together.

How can you assume that every mutation leading to oncogene addiction can really be treated or considered the same? So you're right, with RET, with ALK, with EGFR, the adjuvant setting gave rise to the same Hadar ratio of 0.2 or something like that, kind of fantastic one.

I think we need to keep in mind, and that's why we are so excited today, that KRAS mutations is slightly different.