Transcript

Hello, I'm Dr Hope Rugo from the University of California at San Francisco's Comprehensive Cancer Center, and I'm going to review for you today a few different abstracts that were presented as posters at this year's virtual ASCO 2020 in order to familiarize you with some of the, I think, more important data that we understand now, based on previous studies and further analyses, and also, looking at some of the ongoing studies that may help us understand this area better.

So we saw with excitement that this year we've seen approval of 2 novel agents for the treatment of HER2-positive metastatic breast cancer, and one of these drugs, trastuzumab deruxtecan, was approved in patients who'd received prior treatment in the metastatic HER2-positive setting, based on a single-arm, phase 2 trial called DESTINY-Breast01 and an unmet need.

Of course, when we have a really exciting new agent, we do want to understand how that agent can work in combination with other therapies. And there is data, of course, in the HER2 setting that you have more TILs, or tumor-infiltrating lymphocytes, and some expression of PD-L1.

There's been a lot of interest in testing immunotherapy in this area, and we saw data from Sherene Loi that suggested that patients who had trastuzumab-resistant disease who received a checkpoint inhibitor with pembrolizumab had a response. It was a small number of patients, and the PD-L1-positive patients seemed to have quite durable responses.

There's been a lot of interest in trying to study immunotherapy in HER2-positive disease and quite a number of studies in the neoadjuvant setting, as well as the metastatic setting, that have added checkpoint inhibitors to standard HER2-targeted therapy, capitalizing on the immune response that we already know is important to the efficacy of HER2-targeted antibodies.

Trastuzumab deruxtecan is actually being studied in combination with a number of different checkpoint inhibitors. We had a poster about a trial in progress using trastuzumab deruxtecan in combination with pembrolizumab in metastatic breast cancer or non–small-cell lung cancer (NSCLC), a phase 1b multi-centered trial.

This trial is actually quite interesting, because it is ongoing. It's a trial that is treating patients who have HER2-expressing breast cancer or HER2-expressing or mutated NSCLC. But there's also a group of patients who have HER2-low breast cancer. It's a small number. These are patients who will have 1+ or 2+ disease by IHC and FISH-negative, the group that is being studied in the randomized phase 3 trial.

I'm really looking forward to seeing this trial to establish preliminary efficacy and safety. Hopefully, we'll see data from the earlier combinations of trastuzumab deruxtecan with other immunotherapy agents in the near future as well. This is, I think, quite an interesting area.