Overall Survival With Dato-DXd Fails to Meet Significance in Breast Cancer

Overall survival (OS) with datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance vs investigator’s choice of chemotherapy in patients with hormone receptor (HR)-positive, HER2-low or HER2-negative breast cancer, according to a high-level analysis of the phase 3 TROPION-Breast01 study (NCT05104866).¹

The findings will be shared at an upcoming medical meeting and with regulatory authorities.

“The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to benefit patients. 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,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in a press release.

The study previously met its dual primary end point of progression-free survival (PFS), and these data were presented at the 2023 ESMO Congress and published earlier this month in the Journal of Clinical Oncology. The median PFS was 6.9 months with Dato-DXd vs 4.9 months with chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; P <.0001).^2,3 In the Dato-DXd arm, 37.5% of patients were progression free at 9 months and 25.5% were progression free at 12 months. Comparatively, 18.7% and 14.6% of patients in the chemotherapy arm were progression free at 9 and 12 months, respectively.³

“Consistent PFS benefit was observed across prespecified subgroups, including previous therapies (taxanes/anthracyclines, CDK4/6 inhibitors, and endocrine therapy), geographic region, age, race, and ECOG performance status,” wrote study authors.

Although OS data were not mature at the time of submission, the trend favored Dato-DXd with an HR of 0.84 (95% CI, 0.62-1.14).³

Overall response rate assessed by blinded independent central review was 36.4% with Dato-DXd vs 22.9% with chemotherapy (OR, 1.95; 95% CI, 1.41-2.71), and the median duration of response was 6.7 months (range, 5.6-9.8) vs 5.7 months (range, 4.9-6.8), respectively.

The FDA is evaluating the biologics license application for Dato-DXd in previously treated, metastatic, HR-positive, HER2-negative breast cancer, and a regulatory decision is expected in Q1 2025.⁴

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/3uch9y7r

2. Datopotamab deruxtecan significantly extended progression-free survival versus chemotherapy in patients with HR positive, HER2 low or negative breast cancer in TROPION-Breast01 phase 3 trial. News release. Daiichi-Sankyo. October 23, 2023. Accessed September 23, 2024. https://tinyurl.com/46uzydwa

3. 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 online September 12, 2024. doi:10.1200/JCO.24.00920

4. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer. News release. AstraZeneca. April 2, 2024. Accessed September 23, 2024. https://tinyurl.com/mr4dj53s