Eribulin plus anlotinib in advanced soft tissue sarcoma (ERAS): Updates on efficacy and biomarkers.

Abstract

11502 Background: This study provides an updated evaluation of the efficacy and biomarker analysis of combination therapy using eribulin, a microtubule dynamics inhibitor, and anlotinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced soft tissue sarcoma. Methods: In this multi-center phase II study (ERAS), patients received eribulin (1.1 mg/m² intravenously on days 1 and 8) and anlotinib (12 mg orally once daily on days 1-14) in 21-day cycles for 6-8 cycles, followed by maintenance therapy with anlotinib. Pre-treatment paraffin-embedded tumor samples were subjected to transcriptome sequencing analysis. The efficacy of the combination therapy in the ERAS study was compared to that of patients previously treated with anlotinib monotherapy. Results: As of the cut-off date of December 15, 2024, the median follow-up time was 17.8 months for 30 patients receiving combination therapy with eribulin and anlotinib (9 with leiomyosarcoma, 6 with dedifferentiated liposarcoma, and 15 with other types of sarcomas). In contrast, 87 patients received anlotinib monotherapy, with a median follow-up time of 43.3 months. This cohort comprised 28 patients with leiomyosarcoma, 8 with liposarcoma, and 51 with other types of sarcomas. After 1:2 propensity score matching analysis, compared to anlotinib monotherapy, the combination therapy of eribulin plus anlotinib resulted in a higher progression-free survival rate at 24 weeks (70.0% vs. 31.7%, P = 0.001), significantly improved median progression-free survival (8.5 vs. 4.0 months, P = 0.004), and extended overall survival (not reached vs. 18.4 months, P = 0.035) in patients with advanced soft tissue sarcoma. Transcriptomic data from patients treated with eribulin and anlotinib revealed that tumors with partial response or stable disease exhibited significantly higher levels of lipid metabolism compared to those with progressive disease. Conclusions: The combination therapy of eribulin plus anlotinib demonstrated superior efficacy compared to historical data from anlotinib monotherapy in patients with advanced soft tissue sarcoma. The lipid metabolism level in sarcomas could serve as a biomarker for the efficacy of this treatment regimen, potentially providing new insights into L-type sarcomas. Clinical trial information: ChiCTR2300067650 . Results of a 1:2 propensity score matching analysis. Characteristic Anlotinib monotherapy( n = 60) Eribulin plus Anlotinib ( n = 30) P value Age 0.549 ≥65 years 9 6 <65 years 51 24 Gender 0.648 Woman 37 17 Man 23 13 Pathological subtype 0.654 Leiomyosarcoma/liposarcoma 33 15 Other sarcomas 27 15 Pathological grade - G1/Gx 0 0 G2/G3 60 30 Stage 0.096* Locally advanced 5 7 Metastatic 55 23 Surgery history - No 0 0 Yes 60 30 Radiotherapy history 0.226 No 38 15 Yes 22 15 Chemotherapy history >0.999* No 6 3 Yes 54 27 Progression-free survival at 24 weeks 0.001 No 41 9 Yes 19 21 Response 0.345* Partial response or stable disease 7 6 Progressive disease 53 24 *Fisher's Exact Test.