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

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. SOLTI-1007 NeoEribulin is an open-label, two cohort, conducted in 3 countries at 30 trial centers, phase 2 pharmacogenomic study of single agent eribulin as neoadjuvant treatment for operable Stage I-II HER2-negative breast cancer. Cohort 1 included patients with TNBC and cohort 2 included HR-positive breast cancer. All patients received 4 cycles weeks of eribulin (1.23 mg/kg on Days 1 and 8 of every 21-day cycle). Dose reduction of eribulin to 0.97 mg/kg and 0.62 mg/kg was permitted for patients who developed grade 3 or 4 haematological or non-haematological adverse events and/or omitted of day 8 administration in previous cycle for toxicity. Treatment could be discontinued for a maximum of 14 days and could be resumed if adverse events resolved to grade 1 or below. We did safety laboratory testing (blood count and chemistry) at baseline and day 1 and 8 of every treatment cycle (3 weeks). At Cycle 2 Day1 (±5 days), a core-needle biopsy was mandatory. Surgery was performed between 2 and 5 weeks after the last dose of eribulin. Standard adjuvant chemotherapy was administered according to the physician's discretion. The last safety follow-up visit was done 30 days after surgery. Three tumor samples were obtained during the study: 1) Baseline (SCR); 2) At Cycle 2 Day 1(2W) and at surgery (SUR).