Abstract P1-09-09: Efficacy and gene expression results from SOLTI1007 NEOERIBULIN phase II clinical trial in HER2-negative early breast cancer
Authors: A Prat, V Ortega, P Villagrasa, L Paré, P Galván, M Oliveira, P Nucíforo, A Lluch, S Morales, K Amillano, R Lopez, R Gonzalez, L Manso, J Martinez, A Llombart, L De la Peña, S Di Cosimo, IT Rubio, N Harbeck, J Baselga, J Cortés
Journal: Cancer Research (2017)

Abstract Background: Eribulin is the only cancer agent that has demonstrated a significant prolongation in overall survival on previously treated breast cancer patients. To date, no biomarker exists to prospectively select patients who will derive the maximum benefit from this chemotherapeutic. In the SOLTI1007-NeoEribulin study, we explored, in a prospective clinical trial, the efficacy and the association of pre-treatment expression of RNA in patients with HER2-negative breast cancer treated with neoadjuvant eribulin. Methods: SOLTI1007 is a phase II, open-label, single-arm, exploratory pharmacogenomic study of single agent eribulin as neoadjuvant treatment for stage I-II HER2-negative breast cancer (planned n=100 hormonal receptor-positive [HR+] and n=100 HR-negative). Patients received 1.4 mg/m2 of eribulin intravenously on Days 1 and 8 every 21-day cycle, for 4 cycles. Baseline and post-treatment (surgical) formalin-fixed, paraffin-embedded tissue samples were collected and gene expression profiled. PAM50 intrinsic subtype and the Risk of Relapse based on subtype and proliferation (ROR-P) were evaluated in each time-point. The association of each PAM50 signature and pathological complete response in the breast (pCRB) was evaluated using univariate logistic regression models. Results: Between September 2012 and October 2015, one hundred and seventy-four patients (TNBC n=73 and HR+ n=101) were recruited. Mean age (55.5), stage II (90%), negative axilla (78% and 67%), grade 3 (62% and 26%), mean tumor size (3 cm and 3.6 cm) and mean Ki-67 (61% and 31%). Completion of 4 cycles of eribulin was achieved by 85% of the patients. Grade 3-4 toxicities were observed in 19.54%, mostly due to neutropenia (5.1%) and alopecia (4.02%). The overall pCRB was 5.4%. No significant differences were observed between HR+ and TNBC disease. Distribution of the PAM50 intrinsic subtypes was as follows: Luminal A (n=43, 27.7%), Luminal B (n=42, 27.1%), Basal-like (n=63, 40.6%) and HER2-enriched (n=7, 4.5%). pCRB rates by subtype were the following: HER2-enriched (28.6%, 2/7), Luminal B (7.1%, 3/42), Basal-like (4.8%, 3/63), Luminal A (2.3%, 1/43). pCRB rates significantly (p=0.047) differed when HER2-enriched was compared to the other subtypes (odds ratio = 8.06, 95% CI 1.32-49.1). pCRB rate differed significantly by ROR-P (p=0.006): ROR-P high (17.1%, 6/35), ROR-P med (2.7%, 2/75), ROR-P low (2.2%, 1/45). Ki67 % by IHC did not predict pCRB (p=0.918). Subtype change at surgery occurred in 60% (3/5) HER2-enriched, 44.1% (15/34) of Luminal Bs, 10.3% (4/39) of Luminal A and 5.4% (2/37) of Basal-like tumors. 100% of subtype changes in Luminal B disease were to Luminal A. Conclusions: From a response and biological perspective, patients with HER2-enriched and Luminal B disease may benefit the most from eribulin therapy. Mechanistically, our gene expression data further supports previous preclinical evidence suggesting that eribulin triggers a phenotypic conversion. Citation Format: Prat A, Ortega V, Villagrasa P, Paré L, Galván P, Oliveira M, Nucíforo P, Lluch A, Morales S, Amillano K, Lopez R, Gonzalez R, Manso L, Martinez J, Llombart A, De la Peña L, Di Cosimo S, Rubio IT, Harbeck N, Baselga J, Cortés J. Efficacy and gene expression results from SOLTI1007 NEOERIBULIN phase II clinical trial in HER2-negative early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-09.