Approved Antibody-Drug Conjugates in Breast, Lung, and GI Malignancies

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Transcript:

Benjamin P. Levy, MD: To rewind, I want to make sure, trastuzumab deruxtecan [T-DXd] has approval in breast [cancer] for HER2-positive and HER2-low [disease] [and is] used in both populations. Is that right, Kevin? Did I get that right?

Kevin Kalinsky, MD, MS: Correct. Yes, overall survival [OS].

Benjamin P. Levy, MD: And thenTDM-1 [trastuzumab emtansine] based on OS and both positive and low. So survival advantage in both of those patient populations. Potentially, TDM-1 can be used either in the adjuvant setting or as a sequencing strategy down the line. Is that a fair characterization of breast [cancer treatment]?

Kevin Kalinsky, MD, MS: Yes.

Benjamin P. Levy, MD: Okay. And then in GI [gastrointestinal], third line [there was] a monster benefit in a phase 3 study approved. Interestingly, in lung, it gets approved just in the second line as a single agent based on response rate. And I don’t know, again, when we see there’s this weird metric in lung if you see that response rate of 60% now, PFS [progression-free survival] was close to a year. The durability is pretty remarkable. I can’t remember off the top of my head what the durability of the response is, but we got an approval based on an objective response rate with the lower ILD [interstitial lung disease]. It’ll be interesting to see, I can tell you in lung that these HER2 ADCs [antibody-drug conjugates], because it’s only a sliver of the pie for HER2 exon 20, we are looking at it in HER2 overexpressed. Well, companies are looking at HER2 overexpressed and trying to do or use some of the same modeling in breast. We’ll have to see how this shakes out. I’m dubious of IHC [immunohistochemistry] predicting response rates to these drugs. I have yet to see any good data on this. I’m curious if you’ll see it in gastric and breast, but I just don’t know if IHC is the way we should go with these drugs. We’ll have to see.…

Benjamin L. Musher, MD: …I forgot to say one important thing, with gastric cancer, in this particular trial that had 187 people in it, there was actually a higher percentage of people. Again, they just compared 3+ vs 2+ FISH [fluorescence in situ hybridization] positive because the lower expression wasn’t even included in the study. For what it’s worth, the response rate, and I just looked this up…the response rate was about 60% vs 30%.

Benjamin P. Levy, MD: In the highs and the lows.

Benjamin L. Musher, MD: Yeah, IHC 3+ vs IHC 2+ FISH positive. But they didn’t even include the 1+s. So I don’t know. But at least for the very high vs high-ish, there was a high response rate for these numbers.

Benjamin P. Levy, MD: Yeah. It’s interesting that there are different trends from different LMDs [leptomeningeal disease] and the CNS [central nervous system] penetration maybe that you’re seeing in breast, we’re not seeing it in lung. The overexpression in gastric predicting efficacy is not doing it in lung. It’s really interesting to see how these drugs shake out in different disciplines.

Transcript is AI-generated and edited for clarity and readability.