Soliman et al. report the safety and efficacy of the engineered oncolytic virus T-VEC in combination with standard-of-care anthracycline and taxane chemotherapy as neoadjuvant therapy for early-stage TNBC. The treatment-related toxicities were safe and tolerable. Out of 37 patients, 16 (45.9%) had residual cancer burden (RCB) 0, and an additional 8 patients had RCB1, resulting in a descriptive RCB0–1 rate of 65%. GSEA analysis revealed upregulation of multiple immune signaling pathways, accompanied by increases in effector and memory T cell densities at week 6. Tumors with higher EMT and lower E2F pathway enrichment did not respond well to the therapy.
Contributed by Shishir Pant
ABSTRACT: Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate_=_45.9% and RCB0-1 descriptive rate_=_65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.