Third-line datopotamab deruxtecan improves progression-free survival in previously treated metastatic HR+/HER2- breast cancer compared with chemotherapy

TROPION-Breast01 demonstrated a statistically significant improvement in progression-free survival (PFS) with the TROP2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) compared with chemotherapy. In addition, Dato-DXd presented with a favourable safety profile.

Despite new therapeutic options, failure to endocrine and subsequent chemotherapy or CDK4/6-directed therapy remains a clinical problem. Chemotherapy is widely used for the management of endocrine-resistant HR+/HER2- metastatic breast cancer but is associated with low response rates, poor prognosis, and significant toxicity [1]. The current phase 3 TROPION-Breast01 (NCT05104866) trial compared the efficacy and safety of Dato-DXd with chemotherapy.

TROPION-Breast01 enrolled 732 participants with inoperable or metastatic HR+/HER2- breast cancer, who had progression on endocrine therapy, and who had received 1–2 prior lines of systemic chemotherapy. Participants were randomised 1:1 to receiving Dato-DXd or the investigator's choice of chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). The primary endpoints were PFS and overall survival (OS). Dr Aditya Bardia (Massachusetts General Hospital, MA, USA) presented the first results [2].

At the data cut-off, after a median follow-up of 10.8 months, 93 participants in the Dato-DXd arm versus 39 participants in the chemotherapy arm were undergoing treatment. The median PFS was significantly better in the Dato-DXd arm compared with the chemotherapy arm: 6.9 months versus 4.9 months (HR 0.63; 95% CI 0.52–0.76; P<0.0001). At 9 months, 37.5% versus 18.7% of participants were free of progression. The benefit of Dato-DXd over chemotherapy was observed in all prespecified subgroups, including prior use of CDK4/6 inhibitors. In addition, the overall response rate was increased in the Dato-DXd arm, reaching 36.4% versus 22.9% in the chemotherapy arm. OS data are not yet mature and were not presented.

The rate of grade ≥3 treatment-emergent adverse events was lower in the Dato-DXd arm compared with the chemotherapy arm (21% vs 45%), as were rates for dose reduction (21% vs 30%), and dose interruption (12% vs 25%).

Based on these findings, Dr Bardia concluded that “TROPION-Breast01 demonstrated a statistically significant and clinically meaningful improvement of PFS with Dato-DXd, compared with chemotherapy. In addition, Dato-DXd demonstrated a favourable safety profile.”

1. 
   
   1. Kuderer NM, et al. Nat Rev Clin Oncol. 2022;19:681–697.
   2. Bardia A, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial. Abstract LBA11, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 18 December 202318 December 2023