T-DXd plus pertuzumab was approved in China as first-line treatment for unresectable or metastatic HER2-positive breast cancer.
China’s National Medical Products Administration (NMPA) 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 was supported by findings from the phase 3 DESTINY-Breast09 trial (NCT04784715), which were presented at the
“In DESTINY-Breast09, [T-DXd] in combination with pertuzumab showed a median PFS of more than 3 years and supports the potential for this regimen to become a new standard of care [SOC] in this setting,” Jiang Zefei, MD, president-elect of the Chinese Society of Clinical Oncology and principal investigator in China for the trial, stated in a news release.
DESTINY-Breast09 is a global, multicenter, randomized, open-label phase 3 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.1,2 Patients were randomly assigned 1:1:1 to receive T-DXd plus a pertuzumab-matching placebo (n = 387), T-DXd plus pertuzumab, or THP alone; random assignment 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 received no prior chemotherapy or HER2-targeted therapy for 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, objective response rate (ORR), duration of response (DOR), time to second disease progression (PFS2), and safety. At the interim analysis, with a data cutoff of February 26, 2025, results were reported for the T-DXd plus pertuzumab and THP arms; the T-DXd monotherapy arm remains blinded and will continue to the final PFS analysis.1 The median duration of follow-up was 29.2 months.2
PFS rates by BICR at fixed landmarks favored the T-DXd combination, with 85.9% (95% CI, 81.9%-89.1%) vs 72.4% (95% CI, 67.4%-76.8%) of patients, respectively, remaining progression free at 12 months and 70.1% (95% CI, 64.8%-74.8%) vs 52.1% (95% CI, 46.4%-57.5%) of patients, respectively, remaining progression free at 24 months. By investigator assessment, the median PFS values were 40.7 months (95% CI, 36.5-NC) vs 20.7 months (95% CI, 17.3-23.5), respectively (HR, 0.49; 95% CI, 0.39-0.61; P < .00001), and this PFS benefit was consistent across prespecified subgroups, including among patients with baseline brain metastases (HR, 0.30; 95% CI, 0.12-0.68).
The confirmed ORR was 85.1% (95% CI, 81.2%-88.5%) with T-DXd plus pertuzumab vs 78.6% (95% CI, 74.1%-82.5%) with THP, with complete responses reported in 15.1% vs 8.5% of patients, respectively.¹ The respective median DORs were 39.2 months (95% CI, 35.1-NC) vs 26.4 months (95% CI, 22.3-NC), and 73.3% of patients in the T-DXd arm remained in response at 24 months vs 54.9% of those in the THP arm.1,2 The median investigator-assessed PFS2 was NC with the T-DXd combination vs 36.5 months (95% CI, 36.1-NC) with THP (HR, 0.60; 95% CI, 0.45-0.79; P = .00038).2
The safety profile of T-DXd plus pertuzumab was consistent with the known profiles of the individual agents, with no new safety signals identified.¹ In the safety analysis set, grade 3 or higher possibly treatment-related treatment-emergent adverse effects (TEAEs) occurred in 54.9% of patients treated with the T-DXd combination (n = 381) vs 52.4% of those given THP (n = 382), and TEAEs led to treatment discontinuation in 20.7% vs 28.3% of patients, respectively.²
Adjudicated drug-related interstitial lung disease (ILD) or pneumonitis of any grade occurred in 12.1% of patients in the T-DXd arm vs 1.0% of those in the THP arm.
T-DXd plus pertuzumab is also approved as a first-line treatment for patients with unresectable or metastatic HER2-positive breast cancer
