TVEC: a breakthrough for triple-negative breast cancer patients?
Results from a Phase II trial demonstrate that combining oncolytic virus talimogene laherparepvec (TVEC) with neoadjuvant chemotherapy holds potential as a new triple-negative breast cancer treatment.
Previous research has revealed that triple-negative breast cancer patients with tumors containing a higher number of immune cells are more responsive to chemotherapy. This implies that immunostimulants, such as modified viruses, may improve treatment outcomes.
A few years ago, a group of researchers from Moffitt Cancer Center (FL, USA) decided to test this theory by combining neoadjuvant chemotherapy with a modified oncolytic herpes simplex 1 virus encoding immunostimulatory protein GM-CSF, termed TVEC. Now the results of their Phase II clinical trial have been revealed.
Published in Nature Medicine, the study results assess the effectiveness of TVEC in combination with standard chemotherapy when given to 37 triple-negative breast cancer patients before surgery.
Of the 37 patients that underwent treatment, 45.9% experienced a response, 89% were disease-free 2 years post-treatment and patients with a strong response had no recurrences. Safety data were also similar to standard chemotherapy, excluding higher levels of chills, headaches, fevers and injection site pain.
The researchers also performed a biomarker analysis. They discovered an increased activation of immune cells and immune signaling pathways in tumor samples during the first 6 weeks of treatment. Interestingly, patients with higher densities of CD8 T cells had a better response to therapy compared to patients with fewer CD8 T cells, suggesting that increased immune activation may contribute to better treatment outcomes.
Soliman, a senior member of Moffitt’s Breast Oncology Department, explains that although further research is needed, the future applications of TVEC are promising: “Our results demonstrate that TVEC, when added to systemic chemotherapy, may increase responses in high-risk, early-stage triple-negative breast cancer. There is evidence of robust immune activation within the tumor, and additional investigation of TVEC in combination with current chemoimmunotherapy for triple-negative breast cancer is warranted.”
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Although uncommon, triple-negative breast cancer develops in 15% of women suffering from breast cancer. As its name suggests, it lacks the presence of three types of receptors that are usually detected in breast cancer cells: hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER) and progesterone receptors (PR), meaning the cancer cells emerge as “triple negative” for all three tests.
Typically, triple-negative breast cancers have a poor prognosis and are more difficult to treat compared to other types of breast cancer, as they are more aggressive and have a higher risk of metastasis and recurrence.
Due to the absence of hormone receptors and HER-2, hormonal and HER-2 targeted therapies that are commonly used for other breast cancers are ineffective against triple-negative breast cancer. This leaves limited treatment options available for this cancer, such as chemotherapy, meaning it poses a significant therapeutic challenge
TVEC is approved to treat advanced, late-stage melanoma and the team from Moffitt hopes that their findings will open up new avenues for TVEC in the breast cancer space.