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Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

ABSTRACT: Eribulin prolongs overall survival in patients with pre-treated advanced breast cancer. However, no biomarker exists to prospectively select patients who will benefit the most from this drug. SOLTI-1007-NeoEribulin is a phase II, open-label, two cohort, exploratory pharmacogenomic study in patients with clinical stage I-II HER2-negative breast cancer receiving neoadjuvant eribulin monotherapy treatment. Primary objective was to explore the association of baseline tumor gene expression with pathological complete response in the breast (pCRB) at surgery. Key secondary objectives were pCRB rates in all patients and according to HR status, gene expression changes during treatment and safety. 101 hormonal receptor-positive (HR+) and 73 triple negative breast cancer (TNBC) patients were recruited. The pCRB rates were 6.4% in all patients, 4.9% in HR+ disease and 8.2% in TNBC. The TNBC cohort was interrupted due to a progression disease rate of 30.1%. The pCRB rates differed according to intrinsic subtypes: 28.6% in HER2-E, 11.1% in Normal-like, 7.9% in Luminal B, 5.9% in Basal-like and 0% in Luminal A (HER2-E vs. others odds ratio=7.05, 95% CI 1.80-42.14; p-value = 0.032). Intrinsic subtype changes at surgery occurred in 33.3% of cases, mostly (49.0%) Luminal B converting to Luminal A or Basal-likes converting to Normal-like. Baseline tumor infiltrating lymphocytes (TILs) were significantly associated with pCR. Eribulin showed a good safety profile with a low response and pCRB rates. Patients with HER2-negative disease with a HER2-enriched profile may benefit the most from eribulin. In addition, significant biological activity of eribulin is observed in Luminal B and Basal-like subtypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186102 | GEO | 2021/12/10

REPOSITORIES: GEO

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Project description:The goal of this dataset is to compare the gene expression patterns between primary and metastatic tumors Metastatic cancer patients typically have short survival times and their successful treatment represents one of most challenging aspects of patient care. This poor prognostic behavior is likely due to many factors, including increased clonal heterogeneity, multiple drug resistance mechanisms, and the role of the tumor microenvironment. The AURORA US Metastasis Project was established to collect and molecularly characterize specimens from 55 breast cancer (BC) patients representing 51 primary cancers and 102 metastases. The 153 unique tumors were assayed using RNAseq, tumor/germline DNA exomes and low pass whole genome sequencing, and global DNA methylation microarrays. We found intrinsic molecular subtype differences between primary tumors and their matched metastases to be rare in triple negative breast cancer (TNBC)/Basal-like subtype tumors. Conversely, tumor subtype changes were relatively frequent in estrogen receptor positive (ER+) cancers where ~30% of Luminal A cases switched to Luminal B or HER2-enriched (HER2E) subtype. Clonal evolution studies identified changes in expression subtype coincident with DNA clonality shifts, especially involving HER2 amplification and/or the HER2E expression subtype. Microenvironment differences varied according to tumor subtype where ER+/Luminal metastases had lower fibroblast and endothelial cell content, while TNBC/Basal-like metastases showed a dramatic decrease in adaptive immunity. In 17% of metastatic tumors, we identified DNA methylation and/or focal DNA deletions near HLA-A that were associated with its significantly reduced expression, and with lower immune cell infiltrates. We also identified low immune cell features in brain and liver metastases when compared to other metastatic sites, even within the same patient. These findings have direct implications for the treatment of metastatic breast cancer patients with immune- and HER2-targeting therapies and suggest potential novel therapeutic avenues for the improvement of outcomes for some MBC patients.

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Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

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