Treatment with trastuzumab rezetecan significantly improves progression-free survival (PFS) compared with physician’s choice of chemotherapy among patients with HER2-low advanced breast cancer, according to the phase III HORIZON-Breast06 trial presented at ESMO 2026.
Among chemo-naive patients, as assessed by blinded independent central review (BICR), patients who received trastuzumab rezetecan had a significantly prolonged median PFS than those who received physician’s choice of chemotherapy (16.6 vs 6.8 months). This corresponded to a 75-percent reduction in the risk of disease progression or death (hazard ratio [HR], 0.25; p<0.001). [ESMO 2026, abstract LBA13]
Findings were similar across the overall study population, with a median PFS per BICR of 16.4 months for trastuzumab rezetecan vs 6.8 months for physician’s choice of chemotherapy (HR, 0.27; p<0.001).
Among chemo-treated patients, a longer median PFS was also observed in the trastuzumab rezetecan group than in the physician’s choice of chemotherapy group (13.9 vs 5.6 months; HR, 0.32).
The PFS benefit observed with trastuzumab rezetecan over physician’s choice of chemotherapy was consistent across all prespecified subgroups, regardless of hormone receptor status (median 16.4 vs 6.7 months; HR, 0.24 in the hormone receptor-positive cohort and median 16.5 vs 6.8 months; HR, 0.34 in the hormone receptor-negative cohort).
“Trastuzumab rezetecan demonstrated statistically significant and clinically meaningful improvement in PFS” in both chemo-naive and overall patients, meeting the dual primary endpoint of the study, said Prof Ying Fan from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China.
This trial enrolled 551 patients (median age 55 years) with HER2-low metastatic breast cancer who were randomized in a 1:1 ratio to receive either trastuzumab rezetecan 6.4 mg/kg IV every 3 weeks (n=277) or physician’s choice of therapy (taxanes, eribulin, capecitabine, or gemcitabine; n=274). Of these, 449 were chemo-naive patients and 102 were chemo-treated patients.
Key secondary endpoints
At data cut-off, overall survival (OS) data were still immature, although a favourable trend was observed with trastuzumab rezetecan over physician’s choice of chemotherapy in both the chemo-naive (HR, 0.62) and overall (HR, 0.67) populations.
Furthermore, 12-month OS rates were higher in the trastuzumab rezetecan group than in the physician’s choice of chemotherapy group (92 percent vs 83 percent [chemo-naive patients] and 90.6 percent vs 81.4 percent [overall patients]).
Objective response rate was higher with trastuzumab rezetecan than with the physician’s choice of chemotherapy (75.5 percent vs 41.2 percent), with a longer median duration of response (15 vs 6.8 months).
Safety
Grade ≥3 treatment-related adverse events (TRAEs) occurred in 84.1 percent of patients receiving trastuzumab rezetecan vs 67.9 percent of those receiving physician’s choice of chemotherapy.
In the trastuzumab rezetecan group, the most common grade ≥3 TRAEs were decreased neutrophil count (65.2 percent), decreased white blood cell count (56.5 percent), and anaemia (42.8 percent).
Despite these haematologic toxicities, Fan noted that the safety profile was manageable, noting a low incidence (2.5 percent) of interstitial lung disease with trastuzumab rezetecan.