TROP2-Targeting Antibody-Drug Conjugates

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Transcript:

Benjamin P. Levy, MD: Let’s move on to TROP2. This will be more of a lung and breast [cancer] narrative. TROP2 ADCs [antibody-drug conjugates] are being played around with in our trials and our clinics right now, and we’re trying to figure out how they fit in, in lung. But maybe we can start once again with breast because you guys have sacituzumab govitecan and have been using that. Maybe you can give us a high-level overview, [Dr Kalinsky], of just the ADC for TROP2 and maybe the data supporting the use of this drug.

Kevin Kalinsky, MD, MS: Sure. Sacituzumab govitecan was originally approved for triple-negative breast cancer. It now has approval in ER+ [estrogen receptor–positive] HER2-negative breast cancer and the HER2-low population. So it got approved, triple-negative, based on a phase 1-2, and there was a confirmatory study called the ASCENT study [NCT02574455], in which patients received at least 2 prior lines of therapy. One could have been in the operable setting. And if you had an early relapse, it’s given 2 weeks on and 1 week off. Also, we have the approval for ER+ disease as well based on the TROPiCs-02 study [NCT03901339]. That’s sacituzumab govitecan and is the only approved TROP2 ADC at the moment. But if we all get together this time next year and talk about updates and ADCs, I suspect we’ll be talking about Dato-DXd [datopotamab deruxtecan], which is a TROP2 that also has the deruxtecan payload. I know they’re evaluating this in lung cancer as well. That’s given once every 3 weeks and has a different [adverse] effect profile that I’d be happy to get into, and we should be seeing the results of a randomized phase 3 trial with Dato-DXd sometime within the next year.

Benjamin P. Levy, MD:Kayla, just your impressions of managing patients on sacituzumab. It’s a big race in lung, between Dato-DXd and sacituzumab, right now; it’s highly competitive. So we’re going to start seeing, Rasheda [Persinger, MSN, AGNP-C, AOCNP,] and I will are both going to start seeing these drugs being used in our everyday clinic. So once again, trying to learn from the breast world, maybe you haven’t used Dato-DXd, but what are your experiences with sacituzumab?

Kayla Freeman, DNP, APRN, FNP-C: Yeah, I think saci [sacituzumab] is fairly well tolerated by most of our patients. Diarrhea can be an issue for these patients. So ensuring that, of course, they have Imodium [loperamide]. Talking to them before they start therapy, ensuring that if you get home and it’s not manageable with Imodium, we can send Lomotil [diphenoxylate/atropine]. So talking to them about that up front. Then, of course, neutropenia is a big thing with this drug. We oftentimes are utilizing growth factor after day 1, adding Neulasta [pegfilgrastim] after day 8. Anemias and of course watching hemoglobin, and whether or not these patients need any blood transfusions. Those are the big 3 that come to mind, but overall, it is a fairly well-tolerated drug. Of course, fatigue comes along with your therapies as well. But those are the big ones. Dr Kalinsky, do you have any other [thoughts?]…

Kevin Kalinsky, MD, MS: Yeah, I would stress just a few things. One, all patients lose their hair. Everyone loses their hair. If you look at the report, with sacituzumab every patient loses their hair. The other thing is, as Kayla mentioned, we can see in toxicity it’s quite frequent that we have to utilize growth factors. And then the major distinguishing feature between sacituzumab and Dato-DXd, because Kayla and I have experience with Dato-DXd, given some clinical trials is oral stomatitis. I can’t reiterate [enough] the importance of utilizing oral dex rinse, including preventatively, so that you do not see that in your patients because it can be a challenge for patients. For Dato-DXd the main [adverse] effect to be aware of is the stomatitis.

Benjamin P. Levy, MD:Yeah, I think that Rasheda and I could go on and on about the stomatitis for Dato-DXd. We are struggling with that too. For lung cancer, what’s so interesting is that sacituzumab govitecan was the first ADC ever looked at in lung cancer and published in 2017, and the response rate was only 16% in a highly pretreated group of patients. Then the drug just went off a cliff and no one saw it again and no one used it. What’s interesting now is it’s being resurrected and resuscitated now that the TROP2 story has started again. [Those] data [were] left behind. It was a highly predictable pretreated group of patients. There was durability in some of these responses. There were shifts in industry taking over that drug and trends with the ADCs. The drug trial started, I think, in 2014 for lung. This was almost 10 years ago, and then unfortunately published I think in 2017 or 2018. And then went away. We now have drug trials with sacituzumab govitecan that are ongoing, but I would echo what you said about the Dato-DXd drugs in lung as well.

There are several studies going on with Dato-DXd and lung. One you may or may not hear about in 4 weeks. It’s a direct head-to-head comparison to docetaxel in a phase 3 study. A reminder in lung cancer, sadly, the only drug that’s approved second line for patients without genomic alterations is docetaxel. It remains a grizzly bear that hangs on no matter what you compare it with for some reason. It keeps showing benefit and no drug can knock it off. We will see whether Dato-DXd can knock it off and lead to FDA approval. We’ll find out probably in 4 weeks. It may change the therapeutic paradigm for our patients. But I want to just echo again what Kevin said, which was the stomatitis for Dato-DXd, and the toxicities are very different.

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