Pascual Tomás, Oliveira Mafalda, Villagrasa Patricia, Ortega Vanesa, Paré Laia, Bermejo Begoña, Morales Serafín, Amillano Kepa, López Rafael, Galván Patricia, Canes Jordi, Salvador Fernando, Nuciforo Paolo, Rubio Isabel T, Llombart-Cussac Antonio, Di Cosimo Serena, Baselga José, Harbeck Nadia, Prat Aleix, Cortés Javier
SOLTI Breast Cancer Research Group, Barcelona, Spain.
Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
NPJ Breast Cancer. 2021 Nov 25;7(1):145. doi: 10.1038/s41523-021-00351-4.
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 (pCR) at surgery. Key secondary objectives were pCR rates in all patients and according to HR status, gene expression changes during treatment and safety. One-hundred one hormonal receptor-positive (HR + ) and seventy-three triple-negative breast cancer (TNBC) patients were recruited. The pCR 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 pCR rates differed according to intrinsic subtypes: 28.6% in HER2-enriched, 11.1% in Normal-like, 7.9% in Luminal B, 5.9% in Basal-like and 0% in Luminal A (HER2-enriched 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-like 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 pCR 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.
艾瑞布林可延长经治晚期乳腺癌患者的总生存期。然而，目前尚无生物标志物可用于前瞻性地选择能从该药物中获益最大的患者。SOLTI-1007-NeoEribulin是一项II期、开放标签、双队列的探索性药物基因组学研究，研究对象为接受新辅助艾瑞布林单药治疗的临床I-II期HER2阴性乳腺癌患者。主要目的是探讨基线肿瘤基因表达与手术时乳腺病理完全缓解（pCR）之间的关联。关键次要目的是所有患者以及根据激素受体（HR）状态的pCR率、治疗期间的基因表达变化和安全性。招募了101例激素受体阳性（HR+）和73例三阴性乳腺癌（TNBC）患者。所有患者的pCR率为6.4%，HR+疾病患者为4.9%，TNBC患者为8.2%。TNBC队列因30.1%的疾病进展率而中断。pCR率因内在亚型而异：HER2富集型为28.6%，正常样为11.1%，Luminal B为7.9%，基底样为5.9%，Luminal A为0%（HER2富集型与其他类型的优势比=7.05，95%CI 1.80-42.14；p值=0.032）。手术时内在亚型改变发生在33.3%的病例中，主要是（49.0%）Luminal B转化为Luminal A或基底样转化为正常样。基线肿瘤浸润淋巴细胞（TILs）与pCR显著相关。艾瑞布林显示出良好的安全性，缓解率和pCR率较低。具有HER2富集特征的HER2阴性疾病患者可能从艾瑞布林中获益最大。此外，在Luminal B和基底样亚型中观察到艾瑞布林具有显著的生物学活性。
