Datopotamab deruxtecan shows PFS benefit in patients with HR+/HER2- breast cancer

Treatment with datopotamab deruxtecan (Dato-DXd), an investigational TROP2*-directed antibody-drug conjugate, significantly improves progression-free survival (PFS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, according to the TROPION-Breast01 trial presented at ESMO 2023.

The trial met its primary endpoint, with Dato-DXd demonstrating a statistically significant and clinically meaningful improvement in PFS among previously treated or inoperable patients with HR+/HER2- breast cancer compared with investigator’s choice of chemotherapy, said lead author Dr Aditya Bardia from the Harvard Medical School in Boston, Massachusetts, US. [ESMO 2023, abstract LBA11]

The phase III TROPION-Breast01 trial included 732 patients with inoperable or metastatic HR+/HER2- breast cancer who were randomized to receive either Dato-DXd 6 mg/kg every 3 weeks (n=365) or investigator’s choice of single-agent chemotherapy** (n=367). Patients continued treatment until disease progression, unacceptable toxicity, or other discontinuation criteria.

At a median follow-up of 10.8 months, as assessed by BICR***, the median PFS was significantly longer with Dato-DXd compared with standard chemotherapy (6.9 vs 4.9 months; hazard ratio [HR], 0.63; p<0.0001).

These trends favouring Dato-DXd over chemotherapy were similarly seen in the investigator assessment (median PFS of 6.9 vs 4.5 months; HR, 0.64).

Patients treated with Dato-DXd vs those on chemotherapy also achieved a higher PFS rate as early as 6 months (53.3 percent vs 38.5 percent), which was maintained at 9 months (37.5 percent vs 18.7 percent) and 12 months (25.5 percent vs 14.6 percent).

Bardia highlighted that “in terms of landmark analysis, the 9-month PFS rate [was doubled] … among patients who were on Dato-DXd than those on standard chemotherapy.”

This improvement in PFS with Dato-DXd vs chemotherapy was also consistent across all subgroups, such as age, race, ECOG performance status, and geographic region, as well as number of prior lines of chemotherapy, prior use of CDK 4/6 inhibitor, or prior use of taxane and/or anthracycline, Bardia noted.

At a median follow-up of 9.7 months, there was a trend toward improved overall survival (OS) with Dato-DXd compared with investigator’s choice of chemotherapy (HR, 0.84). However, this result is still immature at the time of this analysis, but the study is continuing to the next planned analysis for OS, said Bardia.

Dato-DXd recipients also had a higher objective response rate than the chemotherapy recipients (36.4 percent vs 22 percent).

In terms of safety, grade ≥3 treatment-related adverse events (TRAEs) occurred at a lower rate in the Dato-DXd arm vs the chemotherapy arm (21 percent vs 45 percent), with fewer TRAEs leading to dose reduction (21 percent vs 30 percent) and interruption (12 percent vs 25 percent).

“This is a bit different from most studies. In general, the rate of AEs is [mostly] higher in the intervention arm as compared to the control arm, but here, the rate of grade ≥3 AEs was lower with Dato-DXd compared with chemotherapy,” Bardia highlighted.

Dato-DXd demonstrated a favourable and manageable safety profile, with no new safety signals, he added.

“Overall, TROPION-Breast01 demonstrated that Dato-DXd provides both improved efficacy and safety compared with standard chemotherapy for patients with HR+/HER2- breast cancer,” said Bardia. “Results support [the drug] as a potential new therapeutic option for [this population].”