TROPION-Breast01: Datopotamab Deruxtecan Improves Progression-Free Survival

In January, the FDA approved datopotamab deruxtecan-dlnk (Datroway; Daiichi Sankyo) for adult patients with unresectable or metastatic/HR-positive, HER2-negative breast cancer who have previously received endocrine-based therapy and chemotherapy.¹

The approval is based on findings in TROPION-Breast01 (NCT05104866), presented at an ESMO Virtual Plenary in February 2025. Aditya Bardia, MD, MPH, FASCO, medical oncologist, UCLA Health, discusses these findings.

This transcript was lightly edited and captions were auto generated.

Transcript

Can you discuss the significance of the progression-free survival (PFS) improvement seen with datopotamab deruxtecan-dlnk?

in January 2025, the FDA granted approval to datapotamab deruxtecan or Dato-DXd, a TROP2-directed antibody-drug conjugate for patients with HR-positive/HER2-negative metastatic breast cancer who had received at least 1 prior line of chemotherapy. This was based on the TROPION-Breast01 study, where patients who received Dato-DXd had a median PFS of about 7 months vs about 5 months with standard chemotherapy. So, there was improvement in PFS; there was also higher response rate seen with Dato-DXd. So, how does this fit into the current treatment paradigm? Any patient who has received 1 prior line of chemotherapy potentially is a candidate for Dato-DXd. This is now the third ADC [antibody-drug conjugate] approved in this setting. The other 2 ADCs are sacituzumab govitecan as well as trastuzumab deruxtecan.

Despite the improved overall response rate and PFS observed, overall survival was similar between the 2 study arms. What factors might explain this?

In TROPION-Breast01, while an improvement in PFS was seen by Dato-DXd, the final overall results, as included in the FDA label, did not show an improvement in overall survival with Dato-DXd compared to standard chemotherapy. There could be multiple reasons as to why, despite an improvement in PFS, an improvement in overall survival was not seen, which could include the fact that trastuzumab deruxetecan is also another ADC approved in this space. And if there's an imbalance in terms of more patients in the control arm getting trastuzumab deruxtecan vs patients who've received Dato-DXd, this imbalance in the use of TD-Xt [trastuzumab deruxtecan]—which we know can improve overall survival—could potentially impact the overall survival results seen in TROPION-Breast01. We see the results in the ESMO Virtual Plenary the second week of February 2025, where detailed results related to overall survival from TROPION-Breast01 [were] will be presented.

Reference

1. Steinzor P. FDA approves datopotamab deruxtecan for HR-positive/HER2-negative metastatic breast cancer. AJMC®. January 17, 2025. Accessed February 14, 2025. https://www.ajmc.com/view/fda-approves-datopotamab-deruxtecan-for-hr-positive-her2-negative-metastatic-breast-cancer