John L. Marshall, MD: There’s more than 1 drug out there though, as you talked about earlier. We have a different approach. We had a very nice review yesterday of some new data about that, and Dr Parikh, you could kind of start us off on HER2 antibodies and just kind of re-drill down on that a bit.

Aparna R. Parikh, MD: Yes, so it’s an entirely different approach of targeting the pathway vs actually using it as your way to give your cytotoxic payload. There’s been a series now of the DESTINY CRC [colorectal cancer] studies and I think a key notable feature, as we’ve mentioned already today, is the allowance of prior HER2-directed therapy. And so the way I’m sort of thinking about this in sequencing patients is that you start with your small molecule and antibody first and then at progression you have the option of using your ADC [antibody-drug conjugate].

John L. Marshall, MD: Do I need to retest?

Aparna R. Parikh, MD: That’s a good question. So I have been.

John L. Marshall, MD: It feels right. The best people do it, and you could maybe wear out the clone.

Aparna R. Parikh, MD: Exactly. And especially I think it was nice to see the less ILD [interstitial lung disease] rate with the lower dosing strategy, but especially if you’re going to go into something that can cause a debilitating AE [adverse event], and in the initial DESTINY CRC studies, we did see some grade 5, too. So I had been retesting to ensure. Again, it’s a really good option I think now for the RAS mutants that pop up as well.

John L. Marshall, MD: These are chemotherapy drugs, right? It has all the chemotherapy feel, it’s smart chemotherapy, but a chemotherapy drug.

Aparna R. Parikh, MD: Yes. But I actually missed a really important point with the ADCs, which is very distinct from breast cancer. There is no activity in the HER2-low patients, and that’s a key distinction in colorectal cancer. It’s really the high patients who are the ones benefiting. So we’re not really getting that same sort of HER2-low bystander effect that we’re seeing in breast cancer. So I know the GI [gastrointestinal] oncologist got excited when they saw what we saw in the breast [cancer] data, but unfortunately, not working for our patients.

John L. Marshall, MD: No standing ovation.

Aparna R. Parikh, MD: No standing ovation for us.

John L. Marshall, MD: For those who don’t know, last year there was a standing ovation in the plenary session for HER2-low breast cancer. One of these days, we GI people will get our standing ovation.

Aparna R. Parikh, MD: I think that’s another reason to think about retesting, right? If expression level matters, even if it is partly suppressed, it may not be the time to bring in this potentially rare, but serious toxicity.

John L. Marshall, MD: That could then challenge the sequence question, too. If you’ve got your hook vs not.

Transcript edited for clarity.