Chemotherapy-free regimen shows early promise for metastatic breast cancer subtype

Researchers at the Icahn School of Medicine at Mount Sinai reported encouraging results from the multicenter ASPIRE clinical trial testing a chemotherapy-free regimen for previously untreated HR-positive, HER2-positive metastatic breast cancer. The study, published in the Journal of the National Cancer Institute, evaluated anastrozole, palbociclib, trastuzumab and pertuzumab as a first-line treatment.

The regimen combines endocrine therapy with drugs targeting two key pathways that drive tumor growth. In the trial, 29 patients received the four-drug combination after an initial dose-finding phase for palbociclib. During the first six months, 97% of patients experienced clinical benefit, defined as tumor shrinkage or disease stabilization.

Median progression-free survival was nearly 25 months. After a median follow-up of approximately 39 months, median overall survival had not yet been reached and 93% of participants were still alive. One patient remained on the regimen for more than six years.

Side effects were consistent with the known profiles of the individual drugs. The most common were neutropenia, low white blood cell counts, diarrhea and anemia. Only one patient discontinued treatment due to side effects, and no treatment-related deaths occurred.

The drugs are administered primarily through oral medication and subcutaneous injection, which researchers say could offer a more convenient option than intravenous chemotherapy, particularly for older adults or those with other medical conditions.

Senior author Dr. Amy Tiersten emphasized that while the findings demonstrate durable responses with a manageable safety profile, they need confirmation in larger randomized clinical trials. The study was relatively small and did not directly compare the regimen with current standard-of-care treatments that combine HER2-targeted therapy with chemotherapy.

Approximately 10% of breast cancers are HR-positive and HER2-positive. Current first-line treatments often involve chemotherapy, which can cause significant short- and long-term side effects affecting quality of life. The investigators are planning additional studies to determine whether the chemotherapy-free regimen can improve outcomes compared with existing standards.

The ASPIRE trial enrolled patients across five clinical sites affiliated with Mount Sinai, NYU Langone Health and Columbia University. The publication appears in JNCI: Journal of the National Cancer Institute (2026), DOI: 10.1093/jnci/djag256.