Dr Viansone on De-Escalating Chemotherapy Type and Duration in HER2-Positive Breast Cancer

“De-escalating chemotherapy to [more quickly proceed to] hormonal therapy, CDK inhibitors, or TKIs is rapidly becoming something that can be the future of de-escalation, not just of the kind of chemotherapy, but also of the duration of chemotherapy.”

Alessandro A. Viansone, MD, a medical oncologist at Gustave Roussy in Villejuif, France and part of the Gustave Roussy Alumni Network, discussed emerging strategies to de-escalate both the type and the duration of chemotherapy in patients with HER2-positive breast cancer, spanning response-adapted approaches such as the phase 2 PHERGain trial (NCT03161353) strategy, genomic tools such as the HER2DX assay, and maintenance data from the metastatic setting.

The central question about HER2-positive breast cancer de-escalation has 2 components, according to Viansone: reducing reliance on anthracyclines and reducing the duration of chemotherapy. For patients who achieve a good and rapid response to treatment, a shorter course of chemotherapy may be sufficient, he said.

PHERGain tested that concept using ¹⁸F-fluorodeoxyglucose PET to identify early responders to neoadjuvant dual HER2 blockade with trastuzumab (Herceptin) and pertuzumab (Perjeta), adapting treatment according to metabolic response and pathologic complete response. PET-based response assessment allowed for a shorter course of chemotherapy before continuing with dual HER2 blockade or monotherapy where feasible, Viansone said.

The same patient selection could be accomplished with a genomic signature, such as HER2DX, or with other assays once they are validated, Viansone noted. Such a test could identify biologically favorable HER2-positive disease that is likely to respond rapidly to chemotherapy, supporting a shorter chemotherapy course, he explained.

Viansone also pointed to indirect support from the metastatic setting, citing maintenance data from the phase 3 HER2CLIMB-05 trial (NCT05132582), in which tucatinib (Tukysa) was added to trastuzumab and pertuzumab as first-line maintenance therapy and significantly improved progression-free survival. Those data reinforce the idea that HER2-positive disease can be controlled with less chemotherapy, according to Viansone.

If chemotherapy can be de-escalated such that patients proceed directly to endocrine therapy, CDK4/6 inhibitors, or TKIs, that approach could become the future of de-escalation, Viansone concluded.