Erika Hamilton, MD, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, Tennessee, shares updated results from the DESTINY-Breast07 trial, highlighting data from the arms investigating first-line trastuzumab deruxtecan monotherapy, and combination with pertuzumab for patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer. At the time of reporting, 75% of patients in the 2 arms remained on-treatment without any progression. The response rates of both arms were in the 80% range, though Dr Hamilton noted that this data was still in early stages. This combination of trastuzumab deruxtecan was feasible and well-tolerated.

Dr Hamilton added that the rate of internalization of trastuzumab deruxtecan into the cancer cells was quicker, and there was a more complete inhibition of HER2 signaling, when in the presence of pertuzumab.

These results were first presented at the 2022 San Antonio Breast Cancer Symposium.

Transcript:

Hello. I'm Dr. Erika Hamilton, and I lead the Breast Cancer Research program at Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee. Recently at San Antonio Breast Cancer Symposium in 2022, we saw updated results from several arms of the DESTINY-Breast07 trial. DESTINY-Breast07 was a first-line trial looking at trastuzumab deruxtecan alone and in different combinations. Really to set the stage, we've seen results from DESTINY-Breast02 presented at San Antonio, and DESTINY-Breast03 presented earlier and updated overall survival. Trastuzumab deruxtecan is now our standard HER2 agent in the second-line setting. DESTINY-Breast07 looks at trastuzumab deruxtecan alone or in combinations in the first-line metastatic HER2-positive setting. Specifically, there were 2 different arms that had interim results presented at San Antonio this year.

These arms were trastuzumab deruxtecan alone or trastuzumab deruxtecan in combination with pertuzumab. These arms aim to enroll 50 in one case or 75 patients, but this was the interim look for safety after the first 20. We ended up with 22 or 23 patients in each arm, depending on the arm that we're talking about. 75% of these patients that were reported are still ongoing on study and have not had any progression. The median treatment duration was about 9 months, and the median follow-up duration was about 10 to 11 months, depending on arm.

In terms of adverse events, we saw what would've been expected. Nausea was really the most common side effect. Interestingly, and reassuringly, it was all grade 1/2 nausea. There were no cases of grade 3 nausea. I really think that we're getting better at treating our patients with prophylactic antiemetics. Currently, what's recommended is at least a 2-drug prophylactic antiemetic regimen, and this appears to be benefiting our patients. We also see alopecia in about 40% of our patients. And the side effect that we did see more commonly in combination with pertuzumab was diarrhea, and this is as expected. Our diarrhea rate with trastuzumab deruxtecan alone was a little bit less than 30%, and in combination with pertuzumab, this was about 65%. Luckily, grade 3 diarrhea was rare, at about 9%, but still obviously a side effect that we're going to have to aggressively manage when we combine with pertuzumab, as the most common side effect of pertuzumab is diarrhea.

In terms of overall response rates, both arms gave us response rates in the 80% range. And again, this is still early. There are still patients in follow up that haven't made it to their second scan, and certainly there are more patients being enrolled into these arms.To look at something like progression-free survival is totally premature at this point. Again, we're only talking about 22 or 23 patients per arm, where 3/4 of them still remain on-therapy, and so it's not possible to calculate a progression-free survival.

There were also some correlative aspects of this study that were presented, and specifically rates of trastuzumab deruxtecan internalization into the cancer cells. And what we saw was that in the presence of pertuzumab, trastuzumab deruxtecan internalization was actually quicker — more brusque. We also saw more complete inhibition of HER2 signaling in the presence of pertuzumab, whether we look at total HER2 or phosphorylating HER2.

So, what does all of this mean? First, it means that the combination with pertuzumab was feasible, pretty well-tolerated with really an increase in diarrhea that will have to be managed. But this sets the stage for other trials that are ongoing with trastuzumab deruxtecan in the first-line setting, where pertuzumab is our current standard of care in combination with trastuzumab and a taxane. It’s certainly encouraging to see this data, and we will have more data from this trial and the randomized first line trial that's currently accruing, looking at trastuzumab deruxtecan, either alone or in combination with pertuzumab in the first-line setting.

Source:

Hamilton E. “Dose-Expansion Study of Trastuzumab Deruxtecan as Monotherapy or Combined With Pertuzumab in Patients With Metastatic Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Breast Cancer in DESTINY-Breast07 (DB-07).” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract PD18-11.