Aditya Bardia, MD, Massachusetts General Hospital, Boston, Massachusetts discusses results from the TROPION-Breast01 trial comparing datopotamab deruxtecan with chemotherapy for patients with inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer who have previously received 1 to 2 lines of chemotherapy.

Results found that datopotamab deruxtecan led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with a favorable and manageable safety profile when compared to chemotherapy in this patient population.

Dr Bardia presented these results at the 2023 ESMO Congress in Madrid, Spain.

Transcript:

Hello, I'm Aditya Bardia, I'm a breast medical oncologist at Massachusetts General Hospital, Harvard Medical School, excited to be here at ESMO 2023. A lot of practice changing studies being presented at ESMO. In the Presidential Session 3, we presented the results of the TROPION-Breast01 study looking at datopotamab deruxtecan versus standard chemotherapy for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

As a brief background, for patients with endocrine-resistant, hormone receptor-positive breast cancer, chemotherapy is the mainstay of management. There are TROP-2 antibody drug conjugates (ADC) being developed or approved which have demonstrated efficacy but are also associated with toxicity like diarrhea, neutropenia, thrombocytopenia. These are toxicities we also see with chemotherapy, myelosuppression, peripheral neuropathy. There's an unmet need for better therapies in this setting.

TROPION-Breast01 looked at a novel TROP-2 ADC called datopotamab deruxtecan (Dato-DXd) and patients who are randomized to Dato-DXd versus investigator’s choice of therapy, which could be eribulin, [vinorelbine], capecitabine, or gemcitabine. The primary end point of the study was progression-free survival (PFS).

In terms of the study results, the study met its primary end point. There was improvement in progression-free survival with datopotamab deruxtecan as compared to standard chemotherapy, hazard ratio of 0.63, so that the 37% risk of disease progression or death with Dato-DXd as compared to standard chemotherapy. If you look at median PFS, it was about 7 months with Dato-DXd. If we look at landmark analysis like 9-month PFS, that was double with Dato-DXd as compared to standard chemotherapy. If you look at response rate, again, that was higher with Dato-DXd, more than 35% as compared to about 20% with standard chemotherapy. In terms of overall survival, again, a trend favoring Dato-DXd as compared to standard chemotherapy, the overall survival results are not mature and we need more follow-up and they'll be presented in the future.

In terms of safety, unlike most other studies in this study, we actually saw that the incidence of grade 3 [adverse events] AEs was lower with Dato-DXd than the control arm. Usually the intervention arm has more AEs than the control arm, but here we actually saw lower AEs with Dato-DXd as compared to the control arm. The AEs that were seen with Dato-DXd were mucositis as well as ocular toxicity such as dry eye. With chemotherapy, myelosuppression including neutropenia and neutropenic fever were the common side effects that we're seeing.

Overall, these results confirm that that Dato-DXd improved progression-free survival, and had a favorable safety profile as compared to standard chemotherapy, and if approved in this setting, would provide another therapeutic option for patients with endocrine-resistant, hormone receptor-positive metastatic breast cancer.

Source:

Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptorpositive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPIONBreast01 trial. Presented at 2023 ESMO Annual Congress; October 20-24, 2023; Madrid, Spain. Abstract LBA11.