Dr Barot on CNS Outcomes With Palbociclib in HER2+ Breast Cancer

“Palbociclib is not something we traditionally think of as effective in the CNS like we think about with abemaciclib. There [is], with HER2-positive disease, a high propensity for CNS metastases. The investigators did a comparison of CNS outcomes, and we saw a decrease in the percentage of patients who [developed] brain metastases, and for patients who already had CNS metastases, we also saw a reduction in CNS progression in favor of the palbociclib [arm] compared with the control [arm]. That was exciting and affirming for this high-risk patient population.”

Shimoli Barot, MD, a breast medical oncologist at Cleveland Clinic, discussed central nervous system (CNS) outcomes from the phase 3 PATINA trial (NCT02947685) and the questions surrounding treatment sequencing for patients with hormone receptor (HR)–positive, HER2-positive advanced or metastatic breast cancer.

Barot explained that palbociclib (Ibrance) is not traditionally regarded as having CNS activity, particularly compared with other CDK4/6 inhibitors, such as abemaciclib (Verzenio). However, because HER2-positive breast cancer has a high propensity to metastasize to the brain, the PATINA investigators conducted an analysis comparing CNS outcomes between the palbociclib and control groups.

The analysis showed that a lower percentage of patients in the palbociclib group developed brain metastases. Among patients who already had CNS metastases, the investigators also observed less CNS progression with palbociclib compared with the control regimen. Barot characterized these findings as encouraging and potentially reassuring for patients at risk of CNS involvement.

Barot also addressed how the PATINA regimen may fit into an increasingly complex first-line treatment landscape following the FDA approval of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta). Unlike the maintenance-based PATINA strategy, T-DXd plus pertuzumab is administered continuously, she noted.

In her practice in the first-line setting, Barot said she may favor T-DXd plus pertuzumab, based on findings from the phase 3 DESTINY-Breast09 trial (NCT04784715), for patients with a high visceral disease burden or CNS metastases. She also raised the possibility of using this ADC-based regimen as induction therapy followed by a maintenance strategy, although data supporting this approach are not yet available.

Another unanswered question is whether palbociclib-based maintenance remains effective after exposure to an ADC, according to Barot. She concluded by stating the need to determine how best to sequence these regimens; identify patients who may still benefit from standard induction with a taxane, trastuzumab (Herceptin), and pertuzumab; and balance potential efficacy gains against the toxicities associated with continuous ADC therapy.