Enhertu Combo May Offer Longer Control for HER2+ Breast Cancer

A potential new first-line treatment option for patients with metastatic HER2-positive breast cancer was highlighted by Dr. Sara M. Tolaney during the 2025 ASCO Annual Meeting.

Tolaney discussed findings from the DESTINY-Breast09 trial. This randomized phase 3 study compared standard first-line treatment — a taxane plus trastuzumab (Herceptin) and Perjeta (pertuzumab), also refered to as THP — with either Enhertu (trastuzumab deruxtecan; T-DXd) plus Perjeta or Enhertu plus placebo,

At the 2025 ASCO Annual Meeting, researchers presented interim results of Enhertu plus Perjeta versus the standard of care regimen. Tolaney explained that this combination nearly doubled progression-free survival — the length of time before the cancer grows or spreads — compared with that of THP. Specifically, patients receiving Enhertu with Perjeta had a progression-free survival of 40.7 months compared with 26.9 months for those receiving THP.

To further discuss these findings, Tolaney, a medical oncologist and senior physician at Dana-Farber Cancer Institute, sat down for an interview with CURE.

She also serves as the chief of the Division of Breast Oncology and director of the Susan F. Smith Center for Women's Cancers. Tolaney is also an associate professor of medicine at Harvard Medical School, located in Boston.

Transcript:

What new data were shared on the DESTINY-Breast09 trial at the ASCO Annual Meeting? What do the new findings mean for patients?

The DESTINY-Breast09 study was a randomized phase 3 trial that evaluated patients with HER2-positive metastatic disease who had not received any prior systemic therapy. It randomized them to receive Enhertu alone, Enhertu with Perjeta, or the standard first-line treatment of Taxane with trastuzumab and Perjeta. [The study] was designed to determine if the Enhertu arms were superior to the current standard of care.

What was presented at the 2025 ASCO Meeting were data from an interim analysis comparing Enhertu and Perjeta to THP. [This] comparison met the predefined criteria for success at the time of the interim analysis, whereas the Enhertu alone arm did not meet the threshold set for success at this very early time point, with very stringent criteria. Therefore, the Enhertu alone arm continues to be blinded, and patients continue to remain enrolled. We will see those data in a future presentation.

We presented the comparison of Enhertu and Perjeta to THP and found that, in essence, the combination of Enhertu and Perjeta almost doubled progression-free survival. This meant cancer was controlled for nearly twice as long as in the control arm. Specifically, the progression-free survival for the TDXD and Perjeta arm was 40.7 months, while for THP, it was 26.9 months. As you can see, this was a substantial difference between the two arms, nearly a 14-month improvement.

Given these very significant improvements in progression-free survival, I believe Enhertu and Perjeta could become a new potential first-line treatment option for patients with metastatic HER2-positive breast cancer.

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.