Phase 1/2 trial of a targeted treatment regimen showed promising activity and manageable side effects in patients with HR-positive, HER2-positive cancer
Researchers at the Icahn School of Medicine at Mount Sinai found that a chemotherapy-free combination of four targeted therapies showed encouraging results in patients with HR-positive, HER2-positive metastatic breast cancer, offering a potential first-line treatment option that may be more convenient for some patients and avoids chemotherapy.
The findings, published in the Journal of the National Cancer Institute, come from the multicentre phase 1/2 ASPIRE clinical trial, which evaluated anastrozole, palbociclib, trastuzumab, and pertuzumab as first-line treatment for patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer. The regimen combines endocrine therapy with medicines that target two key pathways that drive tumour growth, potentially allowing patients to avoid chemotherapy in the initial treatment setting.
“This study demonstrates that a chemotherapy-free treatment approach can produce durable responses while maintaining a manageable safety profile for many patients with this subtype of metastatic breast cancer,” said senior author Amy Tiersten, MD, Professor of Medicine (Hematology and Medical Oncology) and Clinical Director of Breast Medical Oncology at the Icahn School of Medicine at Mount Sinai. “Although these findings need to be confirmed in larger randomised clinical trials, they suggest that some patients may eventually have an effective alternative to chemotherapy as their first treatment.”
Breast cancer is the most frequently diagnosed cancer in women, and approximately 10 percent of breast cancers are HR-positive and HER2-positive. While current first-line treatments often combine HER2-targeted therapy with chemotherapy, chemotherapy can cause significant short- and long-term side effects that affect patients’ quality of life.
The ASPIRE trial enrolled patients with previously untreated HR-positive, HER2-positive metastatic breast cancer across five clinical sites affiliated with Mount Sinai, NYU Langone Health, and Columbia University. Researchers first established the optimal dose of palbociclib before evaluating the four-drug combination in 29 patients.
In the trial, 97 percent of patients experienced clinical benefit during the first six months of treatment. Patients lived a median of nearly 25 months before their disease progressed; median overall survival had not yet been reached at the time of the analysis. After a median follow-up of approximately 39 months, nearly 93 percent of participants were still alive. Several patients also experienced durable responses to treatment, including one who has remained on the regimen for more than six years.
The treatment’s side effects were consistent with those expected from the medications used. The most common were neutropenia (having low levels of a type of white blood cell called neutrophils in your blood), low white blood cell counts, diarrhea, and anemia. Only one patient discontinued treatment because of side effects, and no treatment-related deaths occurred.
“The challenge in treating this type of breast cancer is balancing effectiveness with quality of life,” said Rima Patel, MD, Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine and first author of the study. “Many patients, particularly older adults or those with other medical conditions, may not be ideal candidates for chemotherapy. A targeted regimen that can be given primarily through oral medication and subcutaneous injection could offer a more convenient option while reducing some of chemotherapy’s burden.”
Researchers caution that the study was relatively small and did not compare the regimen directly with current standard treatments. Because of those limitations, the findings should be viewed as hypothesis-generating until confirmed in larger randomized trials.
The investigators are planning additional studies to determine whether the regimen can improve outcomes compared with current standard-of-care treatment.
Source: Mount Sinai
