Enhertu Combo Improves Progression in HER2+ Metastatic Breast Cancer

The combination of Enhertu plus Perjeta showed improvement in progression-free survival versus standard treatment among patients with HER2-positive metastatic breast cancer: stock.adobe.com

First-line treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) plus Perjeta (pertuzumab) demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival compared with taxane, Herceptin (trastuzumab) and Perjeta in patients with HER2-positive metastatic breast cancer, according to a news release from AstraZeneca.

The results were shared following a planned interim analysis of the phase 3 DESTINY-Breast09 trial, the first trial in more than a decade, according to the release, to demonstrate superior efficacy compared with current first-line standard of care across a broad HER2-positive metastatic patient population.

“This is the first trial in more than a decade to demonstrate superior efficacy across a broad HER2-positive metastatic breast cancer patient population compared to the current first-line standard of care,” Susan Galbraith, executive vice president of Oncology Hematology R&D at AstraZeneca, said in the news release. “This is a significant milestone for patients and sets the foundation for Enhertu in combination with Perjeta as an important treatment option in the first-line HER2-positive setting.”

The improvement in progression-free survival was seen with Enhertu plus Perjeta across all pre-specified patient subgroups, the release continued. Notably, overall survival — a key secondary end point of the trial — was not mature at the time of this planned interim analysis. Despite this, investigators noted that interim data showed an early trend favoring Enhertu plus Perjeta versus taxane, Herceptin and Perjeta.

Additionally, a second arm of the study, which is evaluating Enhertu monotherapy versus taxane, Herceptin and Perjeta ,remains blinded to both patients and investigators and will proceed until the final progression-free survival analysis.

“The results from DESTINY-Breast09 reinforce the importance of effectively targeting HER2 to achieve durable disease control early in the treatment of HER2-positive metastatic breast cancer. Building on the positive results seen with Enhertu in the second-line setting, these new findings suggest that starting treatment with Enhertu in combination with Perjeta at the time of metastatic diagnosis delays disease progression, postponing the time until additional treatment may be needed,” Ken Takeshita, global head of R&D at Daiichi Sankyo, concluded in the release.

Data from the combination arm of the DESTINY-Breast09 trial will be presented at an upcoming medical meeting and submitted to regulatory authorities.

More Information, Including the Safety of Treatment

HER2-positive metastatic breast cancer, an aggressive disease characterized by overexpression or amplification of HER2, occurs in approximately 15% to 20% of patients with metastatic breast cancer. Although HER2-targeted therapies have led to improved outcomes, prognosis remains poor, as most patients experience disease progression within two years of first-line treatment with the standard. Additionally, approximately one-third of patients do not receive any further treatment after first-line therapy due to disease progression or death.

To combat these unmet needs in patients, Enhertu is used; it is a specifically engineered HER2-directed antibody-drug conjugate approved for several advanced or metastatic cancers, including HER2-positive, HER2-low and HER2-ultralow breast cancers, as well as HER2-mutant non-small cell lung cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and other HER2-positive solid tumors. Some of these indications are granted under accelerated approval and require confirmatory evidence.

The agent has already received approval in over 75 countries as a second-line treatment for patients with HER2-positive breast cancer, based on findings from the DESTINY-Breast03 trial.

The safety profile of Enhertu combined with Perjeta aligns with the known safety profiles of each agent individually, though serious risks associated with treatment include interstitial lung disease and embryo-fetal toxicity.

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