KEY TAKEAWAYS
- Researchers utilized WES and WTS on pretreatment tumor tissues from HER-2 negative MBC patients in the phase 2 KORNELIA trial to identify biomarkers for eribulin and nivolumab combination.
- The findings link high TMB and B-cell enrichment to positive efficacy and HRD to poor efficacy in eribulin plus nivolumab for HER-2 negative MBC.
The eribulin and immune checkpoint inhibitor (ICI) combination demonstrated sustained responses in HER-2 negative metastatic breast cancer (MBC) patients. Notably, PD-L1 expression did not correlate with efficacy.
Researchers performed a comprehensive analysis, including whole exome sequencing (WES) and whole transcriptome sequencing (WTS), on pretreatment tumor tissues from the phase II KORNELIA trial. They explored WES and WTS to identify potential biomarkers and analyze their association with treatment efficacy.
WES data were obtained from 76 patients, and WTS data from 58. Those with progression-free survival (PFS) ≥ 6 months were categorized as PFS6-responders and the rest as PFS6-nonresponders.
In this study cohort, the PFS6 rate was 34.5%, with PFS6-responders exhibiting higher TMB (median TMB 6.6 vs. 5.1 mut/Mb, p = 0.309). TMB-high patients (≥ 8 mut/Mb) displayed a tendency toward longer PFS compared to TMB-low patients (median PFS 8.0 vs. 4.3 months, p = 0.07).
Comprehensive analysis of homologous recombination deficiency (HRD), including mutational signature 3 and HRD scores, revealed an association between overall HRD and poor response to the combination regimen. High HRD score correlated with lower PFS6 rate (23.7% vs. 50.0%, p = 0.031) and shorter PFS (median 4.2 vs. 6.5 months, p = 0.025).
WTS data highlighted high antigen presentation (AP) gene set enrichment scores in PFS6-responders, correlating with significantly longer PFS. Long responders (≥ 18 months) had a higher proportion of naïve B-cells and plasma cells.
Researchers found a positive correlation between high TMB and B-cell enrichment with effective outcomes in HER-2 negative MBC patients treated with eribulin plus nivolumab. Conversely, HRD was linked to poor efficacy.
These findings underscore the importance of considering biomarker enrichment and refining inclusion/exclusion criteria in future clinical trial designs.
Source: https://jitc.bmj.com/content/11/Suppl_1/A896
Clinical Trial: https://clinicaltrials.gov/study/NCT04061863
Park C, Suh KJ, Kim SH, et al797 Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2 negative metastatic breast cancerJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0797 .
