Dr Dent on the Efficacy of First-Line Dato-DXd in TNBC

“What's remarkable is how consistent the data are.”

Rebecca Dent, MD, MSc, FRCP, deputy chief executive officer (clinical) and a senior consultant at the National Cancer Centre Singapore, discussed key efficacy findings from the phase 3 TROPION-Breast02 trial (NCT05374512) investigating first-line datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) vs investigator’s choice of chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who were ineligible for immunotherapy.

The study met its dual primary end points of progression-free survival (PFS) as assessed by blinded independent central review (BICR), and overall survival (OS), Dent began. Regarding the PFS findings, Dato-DXd demonstrated a statistically significant and clinically meaningful improvement compared with chemotherapy, with a median PFS for the Dato-DXd group (n = 323) of 10.8 months (95% CI, 8.6-13.0) compared with 5.6 months (95% CI, 5.0-7.0) for the chemotherapy group (n = 321), representing a 5.3-month difference and a 43% reduction in the risk of progression or death (HR, 0.57; 95% CI, 0.47-0.69; P < .0001).

The median OS for patients receiving Dato-DXd reached 23.7 months (95% CI, 19.8-25.6) compared with 18.7 months (95% CI, 16.0-21.8) for those who received chemotherapy; Dato-DXd reduced the risk of death by 21% (HR 0.79; 95% CI, 0.64-0.98; P = .0291). This survival benefit observed in the first-line setting is significant because the study population predominantly had a PD-L1 combined positive score of less than 10, according to Dent. She stated that observing such results in this TNBC population and setting had not been seen before these findings.

A remarkable aspect of the data was its consistency across key efficacy measures, Dent emphasized. When evaluating clinical effectiveness, the initial focus often lies on whether a patient is achieving a response, she noted. Dato-DXd achieved more than a doubling of the confirmed objective response rate (ORR) compared with chemotherapy. The ORR for patients receiving Dato-DXd was 62.5% compared with 29.3% for those who received chemotherapy. Furthermore, the study demonstrated a higher complete response rate with Dato-DXd (9.0%) vs chemotherapy (2.5%).

With Dato-DXd, the median duration of response reached 12.3 months (95% CI, 9.1-15.9) compared with 7.1 months (95% CI, 5.6-8.9) for chemotherapy. Despite the median total treatment duration for Dato-DXd being more than double that of chemotherapy (8.5 months, range, 0.7-38.0 vs 4.1 months, range, 0.1-32.0), the rates of grade 3 and serious treatment-related adverse effects were similar between the arms, and discontinuation rates were lower with Dato-DXd.