Molecular Biomarkers of Response to Eribulin in Patients with Leiomyosarcoma

Clin Cancer Res. 2021 Jun 1;27(11):3106-3115. doi: 10.1158/1078-0432.CCR-20-4315. Epub 2021 Apr 1.


Purpose: A randomized phase III study evaluated the efficacy of eribulin versus dacarbazine in patients with advanced liposarcoma and leiomyosarcoma. Improved overall survival (OS) led to approval of eribulin for liposarcoma, but not for leiomyosarcoma.

Experimental design: We explored the molecular profile of 77 archival leiomyosarcoma samples from this trial to identify potential predictive biomarkers, utilizing low-coverage whole-genome and whole-exome sequencing. Tumor molecular profiles were correlated with clinical data, and disease control was defined as complete/partial response or stable disease (RECIST v1.1).

Results: Overall, 111 focal copy-number alterations were observed in leiomyosarcoma. Gain of chromosome 17q12 was the most common event, present in 43 of 77 cases (56%). In the eribulin-treated group, gains of 4q26, 20p12.2, 13q13.3, 8q22.2, and 8q13.2 and loss of 1q44 had a negative impact on progression-free survival (PFS), while loss of 2p12 correlated with better prognosis. Gains of 4q22.1 and losses of 3q14.2, 2q14.1, and 11q25 had a negative impact on OS in patients with leiomyosarcoma receiving eribulin. The most commonly mutated genes were TP53 (38%), MUC16 (32%), and ATRX (17%). The presence of ATRX mutations had a negative impact on PFS in both treatment arms; however, the correlation with worse OS was observed only in the eribulin-treated patients. TP53 mutations were associated with longer PFS on eribulin.

Conclusions: Leiomyosarcoma has a complex genetic background, with multiple copy-number alterations and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of patients with leiomyosarcoma when treated with eribulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • CA-125 Antigen / genetics
  • Carcinogenesis / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • DNA Copy Number Variations
  • Disease-Free Survival
  • Female
  • Furans / pharmacology
  • Furans / therapeutic use*
  • Humans
  • Ketones / pharmacology
  • Ketones / therapeutic use*
  • Leiomyosarcoma / diagnosis
  • Leiomyosarcoma / drug therapy*
  • Leiomyosarcoma / genetics
  • Leiomyosarcoma / pathology
  • Liposarcoma / diagnosis
  • Liposarcoma / drug therapy*
  • Liposarcoma / genetics
  • Liposarcoma / pathology
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics
  • Whole Genome Sequencing
  • X-linked Nuclear Protein / genetics


  • Biomarkers, Tumor
  • CA-125 Antigen
  • Furans
  • Ketones
  • MUC16 protein, human
  • Membrane Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ATRX protein, human
  • X-linked Nuclear Protein
  • eribulin