T-DXd plus pertuzumab was approved in the European Union as first-line treatment for unresectable or metastatic HER2-positive breast cancer.
The European Commission (EC) has approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in combination with pertuzumab (Perjeta) for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer.¹
The decision follows a positive opinion
The approval was supported by findings from the phase 3 DESTINY-Breast09 trial (NCT04784715). In the trial, T-DXd plus pertuzumab reduced the risk of disease progression or death by 44% vs a taxane plus trastuzumab (Herceptin) and pertuzumab (THP; hazard ratio [HR], 0.56; 95% CI, 0.44-0.71; P < .00001). The median progression-free survival (PFS) by blinded independent central review (BICR) was 40.7 months (95% CI, 36.5-not calculable [NC]) with the T-DXd combination (n = 383) vs 26.9 months (95% CI, 21.8-NC) with THP (n = 387).1,2
The safety profile of T-DXd plus pertuzumab has been reported as consistent with the known profiles of the individual agents, with no new safety concerns identified.1
“The combination of [T-DXd] and pertuzumab represents a significant therapeutic advance, with [a median] PFS exceeding 3 years compared [with] approximately 2 years with the current standard of care [SOC], and has the potential to become the new first-line SOC,” Cristina Saura, MD, PhD, of Vall d’Hebron University Hospital and the Vall d’Hebron Institute of Oncology in Barcelona, Spain, as well as a steering committee member and investigator for DESTINY-Breast09, stated in a news release.
T-DXd Plus Pertuzumabin First-Line HER2+ Metastatic Breast Cancer: DESTINY-Breast09 Highlights
On the basis of the DESTINY-Breast09 results, T-DXd plus pertuzumab has been incorporated into the ESMO Clinical Practice Guidelines as a category IA first-line treatment option for patients with metastatic HER2-positive breast cancer, regardless of hormone receptor status.
DESTINY-Breast09 is a global, multicenter, randomized, open-label trial evaluating T-DXd at 5.4 mg/kg, either alone or in combination with pertuzumab, vs SOC THP as first-line treatment in patients with HER2-positive metastatic breast cancer. A total of 1157 patients were randomly assigned 1:1:1 to receive T-DXd plus a pertuzumab-matching placebo, T-DXd plus pertuzumab, or THP; randomization was stratified by prior treatment (de novo metastatic disease vs progression from early-stage disease), hormone receptor status, and PIK3CA mutation status. Eligible patients had not received prior chemotherapy or HER2-targeted therapy for metastatic disease, or had received neoadjuvant or adjuvant HER2-targeted therapy more than 6 months before their diagnosis of advanced or metastatic disease.
The primary end point was PFS by BICR in the T-DXd monotherapy and combination arms. Secondary end points included investigator-assessed PFS, overall survival, overall response rate (ORR), duration of response, pharmacokinetics, and safety. The investigational arm evaluating the efficacy and safety of T-DXd monotherapy vs THP remains blinded and will continue to the final PFS analysis.
According to the United States prescribing information, the confirmed objective response rate by BICR was 87% (95% CI, 83%-90%) with the T-DXd combination vs 81% (95% CI, 77%-85%) with THP.3
