Dato-DXd Hits Key Secondary Efficacy End Points in First-Line TNBC

Datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) produced statistically significant improvements time to first subsequent therapy or death (TFST), time to second progression or death (PFS2), and time to second subsequent therapy or death (TSST) vs investigator’s choice of chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who were ineligible for immunotherapy according to data from the phase 3 TROPION-Breast02 trial (NCT05104866) presented during the 2026 ASCO Annual Meeting.¹

At a median follow-up of 27.5 months (range, 13.3-38.7), the median TFST was 10.9 months (95% CI, 9.5-12.1) with Dato-DXd (n = 323) vs 5.6 months (95% CI, 4.9-6.3) with chemotherapy (n = 321; HR, 0.49; 95% CI, 0.41-0.59). The median PFS2 was 15.6 months (95% CI, 13.3-17.4) vs 11.8 months (95% CI, 10.9-12.8), respectively (HR, 0.61; 95% CI, 0.50-0.74. The median TSST values were 16.7 months (95% CI, 15.2-19.5) and 12.6 months (95% CI, 11.3-13.6), respectively (HR, 0.67; 95% CI, 0.55-0.81).

“The totality of the data support Dato-DXd as a new first-line standard of care for patients with locally recurrent, inoperable, or metastatic TNBC for whom immunotherapy is not an option,” David W. Cescon, MD, PhD, a medical oncologist and clinician scientist at the Princess Margaret Cancer Centre in Toronto, Canada, said during the presentation.

In May 2026, the FDA approved Dato-DXd for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.² The approval was supported by prior data from TROPION-Breast02, which demonstrated that Dato-DXd led to significant improvements in progression-free survival (PFS) per blinded independent central review (BICR) and overall survival (OS) vs investigator’s choice of chemotherapy, with HRs of 0.57 (95% CI, 0.47-0.69; P < .0001) and 0.79 (95% CI, 0.64-0.98; P = .0290), respectively. The regulatory decision marked Dato-DXd as the first TROP-2–directed antibody-drug conjugate (ADC) to gain FDA approval for the frontline treatment of this patient population.

What were the key design characteristics of TROPION-Breast02?

TROPION-Breast02 enrolled patients with histologically or cytologically documented locally recurrent inoperable or metastatic TNBC who had received no prior chemotherapy or targeted systemic therapy in the locally recurrent inoperable or metastatic setting and for whom immunotherapy was not an option.¹ Other key inclusion criteria included having an ECOG performance status of 0 or 1; there was no minimum disease-free interval (DFI).

Patients were randomly assigned 1:1 to receive intravenous Dato-DXd at 6 mg/kg every 3 weeks or investigator’s choice of chemotherapy with paclitaxel, nab-paclitaxel (Abraxane), capecitabine (Xeloda), eribulin mesylate/eribulin, or carboplatin. Patients were stratified according to geographic region (US/Canada/Europe vs other regions), PD-L1 status (combined positive score [CPS] ≥ 10 vs < 10), and disease-free interval (DFI; de novo vs prior DFI of 0-12 months vs prior DFI >12 months).

The dual primary end points were PFS by BICR per RECIST 1.1 criteria and OS. Secondary end points included TFST, PFS2, and TSST.

At baseline, median age was 56 years (range, 27-85) in the Dato-DXd arm and 57 years (range, 23-83) in the chemotherapy arm. Most patients in both arms had PD-L1–low status (CPS < 10; 89% vs 91%), visceral metastases (78% vs 73%), less than 3 metastatic sites (64% vs 67%), and were from other geographic regions beyond the US, Canada, or Europe (63% vs 63%). Nab-paclitaxel was the dominant pre-selected choice of chemotherapy in both arms (56% vs 54%).

How did Dato-DXd effect subsequent treatment patterns?

Most patients in both the Dato-DXd (n = 278) and chemotherapy (n = 313) arms received subsequent therapy, at respective rates of 76% and 74%. ADCs were utilized as subsequent therapy at rates of 21% and 41%, respectively. Subsequent ADCs consisted of sacituzumab govitecan-hziy (Trodelvy; 16% vs 33%), sacituzumab tirumotecan (0% vs < 1%), and fam-trastuzumab deruxtecan-nxki (Enhertu; 8% vs 15%).

“The safety profile of Dato-DXd was manageable and consistent with its known profile and treatment discontinuations were low,” Cescon said. “These improved efficacy outcomes translated to meaningful and sustained improvements in quality of life [with Dato-DXd] vs chemotherapy.”

Disclosures: Cescon holds consulting or advisory roles with AstraZeneca; Daiichi Sankyo Europe GmbH; Exact Sciences; GenomeRx; Gilead Sciences; GlaxoSmithKline; Lilly; Merck; Novartis; Pfizer; Roche/Genentech; and SAGA Diagnostics. He received research funding from AstraZeneca (Inst); GenomeRx (Inst); Gilead Sciences (Inst); GlaxoSmithKline (Inst); GRAIL (Inst); Guardant Health (Inst); Inivata (Inst); Knight Therapeutics (Inst); Merck (Inst); PearBio (Inst); Pfizer (Inst); ProteinQure (Inst); RayzeBio (Inst); and Roche/Genentech (Inst). His patents, royalties, and other intellectual property include Patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene.

Supported in part by AstraZeneca and Daiichi Sankyo, content independently developed by OncLive.

References

1. Cescon DW, Traina TA, Schmid P, et al. First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: additional efficacy endpoints from the TROPION-Breast02 study. J Clin Oncol. 2026;44(suppl 16):1002. doi:10.1200/JCO.2026.44.16_suppl.1002
2. Datroway approved in the U.S. as first TROP2 directed antibody drug conjugate for first-line treatment of patients with metastatic triple negative breast cancer who are not PD-1/PD-L1 inhibitor candidates. News release. Daiichi Sankyo. May 22, 2026. Accessed June 3, 2026. https://daiichisankyo.us/web/dsi/press-releases/-/article/datroway-approved-in-the-us-as-first-trop2-directed-antibody-drug-conjugate-for-first-line-treatment-of-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-pd-1pd-l1-inhibitor-candidates