Dr Conlin on Individualizing First-Line and Maintenance Strategies for HER2+ Metastatic Breast Cancer

“Now that we have great data showing that patients with baseline CNS metastases do well with upfront T-DXd plus pertuzumab, patients with new metastatic HER2-positive disease should get an MRI to know who they are.”

Alison K. Conlin, MD, a medical oncologist at the Providence Cancer Institute Franz Clinic, discussed how to individualize first-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta), as well as the optimal use of maintenance strategies, for patients with HER2-positive metastatic breast cancer, including those with central nervous system metastases.

Her insights were based on discussions held during the 2026 Bridging the Gaps in Breast Cancer Meeting.

The phase 3 DESTINY-Breast09 trial (NCT04784715) showed impressive progression-free survival outcomes with T-DXd plus pertuzumab, Conlin said, noting that these data are compelling enough to discuss with patients. At the same time, maintenance therapy strategies remain attractive given the data from the phase 3 PATINA (NCT02947685) and HER2CLIMB-05 (NCT05132582) trials, she noted. Conlin said she feels strongly about upfront T-DXd use for certain patient populations, such as those with central nervous system (CNS) metastases, and hopes future trial designs will identify which patients can transition to maintenance therapy and when. For now, she said it is fair to treat until progression or toxicity, and also fair to use an induction-maintenance approach in some patients.

Given the positive results of an exploratory DESTINY-Breast09 analysis of patients with baseline brain metastases that favored T-DXd plus pertuzumab, patients with newly diagnosed metastatic HER2-positive disease should undergo MRI to identify whether they have CNS involvement, Conlin explained. After T-DXd, a HER2 TKI, such as tucatinib (Tukysa), is probably the next best regimen to maintain sensitivity, she said, although patients with CNS metastases have inferior outcomes after T-DXd.

Treatment goals and quality-of-life priorities should guide HER2-positive breast cancer decision-making, as most patients want to live as long as possible while feeling as good as possible, according to Conlin. Quality-of-life (QOL) data from DESTINY-Breast09 showed that patients had god QOL outcomes through cycle 9, including good fatigue and pain scores, she noted. However, a frail older patient may not be the best candidate for an aggressive upfront regimen, whereas some patient populations may tolerate an induction-maintenance approach better, Conlin concluded.