Evolution of Precision Medicine in Non–Small Cell Lung Cancer - Episode 11
Edward Kim, MD, MBA, summarizes recent data for HER2-mutated in non–small cell lung cancer (NSCLC) presented at the American Society of Clinical Oncology 2021 annual meeting.
Benjamin Levy, MD: Let’s move on to HER2 [human epidermal growth factor receptor 2], another potential actionable mutation. We’ve got some really exciting drugs. Ed, do you want to give us the HER2 story, where we are with some of the therapies, and what you’re most excited about with some of these drugs?
Edward Kim, MD, MBA: Yes. I’m just following up on the breast cancer theme this morning. It’s remarkable about what we’re discussing compared with 10 or even 5 years ago in lung cancer. We have a couple of drugs that target HER2 mutations. One of them is trastuzumab deruxtecan. That’s an anti-HER2 plus TOPI inhibitor. There have been data in patients from the DESTINY-Breast01 study, where they had to have a HER2 mutation. It’s phase 2, over 70% response rates, which is incredible. Even if they looked at other populations within it: 62% PFS [progression-free survival], 14 months in multiple lines. It’s incredible stuff, so it’s been something that has been noticed.
We’ve also got the TDM-1, or trastuzumab emtansine. That’s the HER2-targeted antibody-drug conjugate. This is in patients with HER2 overexpression. It’s a little different from the HER2 mutations. When they reported this study, of 49 patients, they looked at 2+ or 3+. That stuff drives me crazy. It drives me crazy in the breast world. It drives me crazy even more in the lung world. It brings me back to bad memories of all the EGFR expression stuff that went on and probably delayed the advances in mutations into the clinic by at least 5 years because we were arguing about H scores and expression levels. Hopefully, you were all young enough to have missed that whole period in lung cancer.
Benjamin Levy, MD: Except Alex.
Edward Kim, MD, MBA: Except Alex. Alex, he’s scarred. I know, he’s like me. True to form, they found a 20% response rate. In those who were IHC [immunohistochemistry] 3+, there were 4 responses and none in 2+. That 1+ is going to make a difference between 2 and 3. The conclusions were fair, that a better target population is needed who this should go to. We don’t want to just jump in and throw anything. We don’t want to get back to the days of second-line lung cancers we’ve discussed before, where anything gives us a response rate, a modest one. Then for poziotinib, a TKI [tyrosine kinase inhibitor] that targets EGFR, HER2, exon 20 mutants in phase 2, 90 patients had been reported. Response rate was almost 30%, 28%. An evaluable population was 35%. PFS was 5½ months. But there were 12% of patients who discontinued therapy, there’s some toxicity associated. We always have to be careful with that. More drugs to the armamentarium, another target that we’re going to have to pay attention to when we’re in clinic, just as you all are talking about going back to the old reports and it’s deciding which 1 it is. Lung cancer is the model for precision medicine. I don’t think anybody could argue with that.
Benjamin Levy, MD: Nice overview. The trastuzumab deruxtecan story is compelling. I’d be interested to see when we get an FDA approval of that based on some of the activity we saw in patients with HER2-mutated lung cancer. Ed, how do you use HER2 in your practice? What do you do for these patients? Do you try to give them off-label TDM-1 [trastuzumab emtansine]? Do you give them chemo–I/O [immuno-oncology]? How do you leverage this information and use it every day?
Edward Kim, MD, MBA: TDM-1 [trastuzumab emtansine] I’m not so crazy about, honestly. Sometimes it’s hard to get that covered off-site. When we have multiple treated patients—at my old place we had ASCO TAPUR, so we’d try to at least put them in a clinical trial that way—I don’t mind giving these folks chemotherapy and I/O. I don’t know if it’s any better or worse. The jury is still out. I’d love to give them the DESTINY-Breast01 study or have that open for them, but we don’t have that, unfortunately. It’s just a wait and see. We were in the process of opening poziotinib at my old place. That was at [The University of Texas] MD Anderson [Cancer Center]. It’s limited right now. We’re waiting.
Benjamin Levy, MD: Great overview.
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