Dr Tolaney on Questions Regarding Treatment Duration in HER2+ Metastatic Breast Cancer

“These data did help inform a future study design. Unfortunately, they do not answer the question of how long you need to treat, but it'll be nice to get more data to help us understand what happens if you switch patients to a maintenance strategy after 1 year of upfront treatment.”

Sara M. Tolaney, MD, MPH, a senior physician, chief of the Division of Breast Oncology, and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discussed the potential clinical implications of a depth-of-response analysis from the phase 3 DESTINY-Breast09 trial (NCT04784715) evaluating first-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) in patients with HER2-positive metastatic breast cancer.

Tolaney began by noting that the central message from these findings, which were presented at the 2026 ASCO Annual Meeting, is that depth of response appears to matter, though achieving it requires time. In general, it takes approximately 8 or 9 months to reach a complete response or deep partial response, and potentially up to 24 months to hit nadir, she explained. Tolaney observed that a lingering question in the field is whether patients need to continue T-DXd plus pertuzumab until the time of progression, as was done in DESTINY-Breast09.

She acknowledged that the trial’s design cannot answer this question, since investigators do not know whether treating a patient with upfront T-DXd plus pertuzumab until a deep response and then transitioning to a maintenance regimen would yield outcomes comparable with those seen with continued cytotoxic therapy. Nevertheless, Tolaney emphasized that the depth-of-response data directly informed the design of a subsequent trial, which plans to administer approximately 1 year of upfront T-DXd plus pertuzumab before switching to a maintenance regimen of trastuzumab (Herceptin), pertuzumab, endocrine therapy, and palbociclib (Ibrance), Tolaney detailed. This single-arm trial, designed for patients with estrogen receptor– and progesterone receptor–positive disease who have received 18 to 24 cycles of upfront therapy before transitioning to maintenance therapy, is expected to open in the fall of 2026.

Tolaney concluded that although the DESTINY-Breast09 depth of response analysis data did not resolve the question of optimal treatment duration, they have supported future research that may help clarify outcomes with the addition of a maintenance strategy.

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