KEY TAKEAWAYS
- The phase I/II trial aimed to evaluate the efficacy of TVEC/NACT in early-stage TNBC.
- RNA sequencing was used to analyze tumor tissue. The data was aligned to the human genome HG19, and gene expression was evaluated using HTSeq and DEseq2.
- The study concluded that genomic alterations, including an EIF2A SNP, may predict response to OV plus NAC in TNBC.
Talimogene laherparepvec (TVEC) is an engineered oncolytic virus (OV) approved for melanoma treatment. Researchers aimed to evaluate the combined efficacy of TVEC and neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancers (TNBC).
The study used transcriptomic RNA sequencing to analyze tumor tissue (Illumina TruSeq RNA exome kits). Read adapter detection was performed using BBMerge (v37.88) and removal by cutadapt (v1.8.1). STAR (v2.5.3a) facilitated gene expression alignment to HG19, while HTSeq (v0.6.1) determined read counts at the gene level using Gencode gene model v19. Differential expression analysis was carried out using DESeq2 (v1.38.2). For single nucleotide polymorphism (SNP) data search, Ensembl was utilized [Moffitt Molecular Genomics core].
The result demonstrated that tumor mutation burden was not significantly different between pathologic complete response (pCR) and non-pCR samples (median 227 vs 222 mut/MB, P= .11). Top 5 upregulated non-immunoglobulin genes associated with pCR were MYBL1, DNAH8, NR2E1, FGFR2, and SLC12A1 (FDR < 1%). EIF2A gene SNP (c.C290G, p.T97S) top variant associated with response 21/37 samples; (non-pCR = 17/21 vs. pCR = 4/21, FDR < 1%). Significance remained unknown, observed in 17% of Black, 35% of White, and 46% of Asian individuals. Inferior response correlates with lower EIF2A pathway activation.
The study concluded that genomic alterations in EIF2A may predict response to OV plus NAC in TNBC. Further research is needed to validate these findings.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.598
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02779855
Hatem Hussein Soliman, Hyo S. Han, Blaise Mooney, Ricardo L Costa, Marie Catherine Lee, Bethany Niell, Alec Chau, Shannon Falcon, Aixa Elena Soyano Muller, Avan J. Armaghani, Nazanin Khakpour, Robert J Weinfurtner, Susan Hoover, John Kiluk, Christine Laronga, Marilin Rosa, Hung T. Khong, and Brian J. Czerniecki. DOI: 10.1200/JCO.2023.41.16_suppl.598 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 598-598.
