Dato-DXd Misses OS End Point in TROPION-Breast01 Trial of HR+ Breast Cancer

Previously, datopotamab deruxtecan showed statistically significant and clinically meaningful improvement in progression-free survival in the same patient population, at a median follow-up of 10.8 months.

Datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in the final overall survival analysis in patients with metastatic HR-positive, HER2-low, or HER2-negative breast cancer, according to findings from the TROPION-Breast01 phase 3 trial (NCT05104866).¹

No new safety concerns were identified in the updated analysis. Datopotamab deruxtecan continued to show lower rates of grade 3 or higher treatment-related adverse events (TRAEs) compared with chemotherapy. Rates of interstitial lung disease (ILD) remained low, and there were no new grade 3 or higher ILD events.

“The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients,” Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, stated in the press release.¹ “Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for datopotamab deruxtecan in breast cancer.”

Previously, datopotamab deruxtecan showed statistically significant and clinically meaningful improvement in progression-free survival in the same patient population, at a median follow-up of 10.8 months.² Dato-DXd was associated with a 37% reduction in risk of progression or death when compared with investigator’s choice of chemotherapy (ICC), with a hazard ratio (HR) of 0.63 (95% CI, 0.52-0.76; P <.0001). The median PFS by blinded independent central review was 6.9 months (95% CI, 5.7-7.4) with Dato-DXd vs 4.9 months (95% CI, 4.2-5.5) with ICC. The 9- and 12-month PFS rates in the Dato-DXd arm were 37.5% and 25.5%, respectively; in the ICC arm, these rates were 18.7% and 14.6%, respectively.

In the interim overall survival data, a slight trend of improvement was observed in the Dato-DXd arm, with an HR of 0.84 (95% CI, 0.62-1.14). Overall response was observed in 36.4% of patients who received Dato-DXd vs 22.9% of those who received ICC, with an odds ratio of 1.95 (95% CI, 1.41-2.71). The median duration of response was higher in the Dato-DXd arm (6.7 months) than in the ICC arm (5.7 months).

Treatment-related adverse events were observed in 93.6% of patients who received Dato-DXd and 86.3% of patients who received ICC. Grade 3 or higher TRAEs were significantly lower in the Dato-DXd arm (20.8%) than in the ICC arm (44.7%). Serious TRAEs were observed in 5.8% of patients on Dato-DXd vs 9.1% of those on ICC. For patients who received Dato-DXd vs ICC, the most common any-grade TRAEs were nausea (51.1% vs 23.6%), stomatitis (50% vs 13.1%), alopecia (36.4% vs 20.5%), and neutropenia (10.8% vs 42.5%).

The study was limited to patients with inoperable or metastatic HR+/HER2- breast cancer who had received 1 or 2 previous lines of chemotherapy in the inoperable/metastatic setting. Patients in the study were required to be at least 18 years of age and have an ECOG performance status of 0 or 1.

“Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes,” Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, stated in the press release.¹ “We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with Enhertu and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit.”

References

1. Datopotamab deruxtecan final overall survival results reported in patients with metastatic HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial. News release. AstraZeneca. September 23, 2024. Accessed September 23, 2024. https://tinyurl.com/2ajspppy
2. Bardia A, Jhaveri K, Im S, et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor–positive human epidermal growth factor receptor 2–negative breast cancer: primary results from TROPION-Breast01. J Clin Oncol. Published September 12, 2024. doi:10.1200/JCO.24.00920