A team from the Icahn School of Medicine at Mount Sinai (United States) has detected very positive results with a combination of four targeted therapies, without the need for chemotherapy, in patients with metastatic breast cancer with positive hormone receptors (HR) and HER2 positive. This approach could become a more comfortable initial treatment option for certain patients and allow them to forgo chemotherapy.
The data, collected in the 'Journal of the National Cancer Institute', comes from the multicenter phase 1/2 clinical trial "ASPIRE", in which anastrozole, palbociclib, trastuzumab, and pertuzumab were analyzed as first-line therapy in women with HR positive and HER2 positive metastatic breast cancer.
The therapeutic scheme combines endocrine treatment with targeted drugs against two key pathways involved in tumor proliferation, which opens the door to avoiding chemotherapy in the initial approach to this subtype of tumor.
"This study demonstrates that a therapeutic approach without chemotherapy can produce durable responses and maintain a manageable safety profile in many patients with this subtype of metastatic breast cancer," stated the lead author, Amy Tiersten, MD, professor of Medicine and clinical director of Breast Oncology at the Icahn School of Medicine at Mount Sinai.
"Although these results need to be confirmed in larger randomized clinical trials, they suggest that some patients may have an effective alternative to chemotherapy as first treatment in the future," Tiersten added.
Breast cancer is the most common tumor in women, and about 10 percent of cases correspond to HR positive and HER2 positive tumors. Standard first-line treatments usually combine targeted therapies against HER2 with chemotherapy, but the latter is associated with significant adverse effects, both immediate and long-term, that can diminish quality of life.
In the "ASPIRE" trial, patients with HR positive and HER2 positive metastatic breast cancer without prior treatment were included, treated at five centers linked to Mount Sinai, NYU Langone Health, and Columbia University. First, the appropriate dose of palbociclib was defined, and subsequently, the complete combination of the four drugs was tested in 29 patients.
97% of patients obtained clinical benefit in six months
In the study, 97 percent of the participants showed clinical benefit during the first six months of therapy. The median time to disease progression was almost 25 months, while the median overall survival had not yet been reached at the time of the analysis.
With a median follow-up of nearly 39 months, almost 93 percent of the women were still alive. Several patients exhibited prolonged responses, including one who has been on the same therapeutic regimen for more than six years.
The observed adverse effects were consistent with the known safety profile of these medications. Among the most common were neutropenia (decrease in neutrophils), overall reduction of white blood cells, diarrhea, and anemia. Only one patient discontinued treatment due to side effects, and no deaths related to the therapy were recorded.
"The challenge in treating this type of breast cancer is to balance efficacy with quality of life," noted Rima Patel, MD, assistant professor of Medicine (from the Icahn School of Medicine and first author of the study).
"Many patients, especially older ones or those with other illnesses, may not be ideal candidates for chemotherapy. A targeted regimen that can be administered mainly through oral medication and subcutaneous injection could offer a more comfortable option and reduce some of the burden associated with chemotherapy," emphasized Patel.
The authors remind that this is a small study and without direct comparison to current standard therapies. Therefore, they emphasize that the findings should be interpreted as hypothesis-generating until validated in larger randomized trials.
Currently, the research group is designing new studies to determine if this regimen can improve outcomes compared to the current standard treatment.