Chemotherapy-free regimen shows promise in metastatic breast cancer

Across five clinical sites affiliated with Mount Sinai, NYU Langone Health and Columbia University, researchers tested a way to treat a difficult form of metastatic breast cancer without chemotherapy. The ASPIRE phase 1/2 trial combined four targeted medicines in 29 patients whose tumors were hormone receptor-positive and HER2-positive and who had not yet been treated for metastatic disease.

The treatment paired anastrozole, an endocrine therapy, with palbociclib, trastuzumab and pertuzumab. In practical terms, it combines hormone treatment with medicines aimed at two pathways that drive tumor growth. The approach could allow some patients to avoid chemotherapy in the initial treatment setting, while relying mainly on oral medication and subcutaneous injection.

The early results were encouraging but came from a small group. 97% of patients experienced clinical benefit during the first six months, and disease progression occurred after a median of nearly 25 months. After a median follow-up of approximately 39 months, nearly 93% of participants were still alive; median overall survival had not yet been reached. One patient had remained on the regimen for more than six years.

The side effects matched those expected from the drugs, with neutropenia, low white blood cell counts, diarrhea and anemia among the most common. Only one patient stopped treatment because of side effects, and no treatment-related deaths occurred. Those findings suggest a manageable safety profile for many patients, but they do not establish that the regimen is better than chemotherapy-based care.

So what changes for patients? Older adults and people with other medical conditions who are not ideal candidates for chemotherapy could eventually have a more convenient first-line option, with less of chemotherapy's burden. The evidence is not ready to support that change yet: the Mount Sinai team says the trial was relatively small, did not directly compare treatments, and needs confirmation in larger randomized studies.