by A recent clinical trial conducted by Vanderbilt researchers has demonstrated the efficacy of combining atezolizumab, an immunotherapy, with carboplatin, a chemotherapy drug, in the treatment of metastatic triple-negative breast cancer. The study also aimed to identify biomarkers that could predict patient response to immunotherapy.
In 2019, atezolizumab became the first approved immunotherapy for breast cancer. However, two years later, its efficacy was called into question when additional data from a follow-up trial failed to confirm its benefits. The drug had initially been approved for use in combination with the chemotherapy drug nab-paclitaxel for metastatic PD-L1-positive triple-negative breast cancer.
The Vanderbilt clinical trial involved combining atezolizumab with carboplatin, a different chemotherapy drug that functions in a distinct manner from nab-paclitaxel. The combination therapy significantly increased the progression-free survival and overall survival rates of patients with metastatic triple-negative breast cancer.
The combination of atezolizumab with carboplatin extended the median progression-free survival from 2.2 months to 4.1 months compared to carboplatin alone. The overall survival rate also improved from a median of 8.6 months to 12.6 months for patients receiving the combination therapy.
The phase II randomized clinical trial involved 106 patients from diverse ethnicities and was conducted at six cancer centers through the Translational Breast Cancer Research Consortium.
Vandana Abramson, MD, co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center, highlighted the significance of the study’s ability to collect biopsies from all participants, enabling researchers to understand the factors that influence response to treatment.
The researchers theorized that atezolizumab would be more effective when combined with carboplatin due to the latter’s capacity to cause DNA changes and generate neoantigens that may stimulate an immune response. In contrast, nab-paclitaxel functions by preventing cancer cells from dividing.
The study also investigated the four subtypes of triple-negative breast cancer, which were identified based on refined classification. These subtypes include two basal-like subtypes, a mesenchymal subtype, and a lumen androgen receptor-expressing subtype. Results showed that patients with luminal androgen receptor-expressing tumors, similar to estrogen receptor-positive disease, displayed less benefit from immunotherapy.
Interestingly, patients with higher body mass indexes and uncontrolled blood glucose levels experienced greater benefits from the combination therapy. The researchers speculated that these patients may have an increased number of immune cells targeted by anti-PD1/PD-L1 therapies. Additionally, a lower risk of disease progression was associated with high mutation burden and increased tumor-infiltrating lymphocytes.
The study also revealed that patients benefited from atezolizumab even if their tumors were PD-L1 negative. Furthermore, tumors with high mutation burdens and the presence of immune cells within or around the tumor exhibited a greater response to immunotherapy.
The combination therapy was generally well-tolerated, with side effects consistent with previous reports for atezolizumab. The most common observed complications included low blood platelet counts, anemia, lymphocytopenia, nausea, fatigue, and increased liver enzymes.
The successful outcome of this study was made possible by the collaborative efforts of breast cancer patients who contributed their time and biospecimens. The study spanned a network of cancer centers within the Translational Breast Cancer Research Consortium and involved a multidisciplinary team of healthcare professionals and researchers.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
