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Soft Tissue Tumors

(P 354) UNEXPECTED RESPONSE TO ERIBULIN IN A REFRACTORY LEIOMYOSARCOMA PATIENT WITH HEREDITARY P53 MUTATION

    Author(s)

  • Benjamin C. Powers, MD

    Associate Professor, Division of Medical Oncology
    The University of Kansas Health System
    Leawood, Kansas, United States

    • Co-Author(s)

  • JH

    Julie Hamlin, APRN

    Nurse Practitioner
    The University of Kansas Health System
    Overland Park, Kansas, United States

Objective: To describe an unexpectedly nice response to eribulin in a heavily pre-treated patient with leiomyosarcoma and germline p53 mutation

Methods: At the age of 57, a patient was complaining of upset stomach associated with nausea, abdominal pain and fatigue.
In Feb 2023, CT imaging showed multiple bilateral pulmonary nodules, lytic lesion in the T9 vertebral body, multifocal hepatic masses, mild periportal adenopathy, several subcutaneous nodules, and a lytic lesion of medial right iliac bone. Liver mass biopsy done Feb 2023 showed leiomyosarcoma. NGS of the liver mass showed RB1 and TP53 mutations as well as BCL6 rearrangement. It was microsatellite-equivocal with low tumor mutational burden. PDL-1 0%. PET showed widely metastatic disease as well as a large left thigh leiomyosarcoma, not appreciated previously.
Over the next year, she tried single-agent doxorubicin, combo of doxorubicin/dacarbazine, pazopanib, and trabectedin. She also had radiation to the left thigh mass. Due to ongoing progression, she was started on fifth-line therapy with eribulin late April 2024.

Intriguingly, she found out her nephew died of leiomyosarcoma at the age of 24 and her nephew's daughter was found to have hereditary p53 mutation. Despite her age, due to this family history, we sent her to genetic counseling in Feb 2024; she was found to have a pathogenic germline p53 mutation to match that found in her tumor NGS.

Results: She has maintained on eribulin since, with latest CT May 2025 showing more or less stability (>1 year since starting).
She is having more neuropathy and constipation the longer the drug is used, but certainly this drug has managed her disease a lot longer than expected.

Conclusion: Wozniak et al showed that p53 mutations were associated with significantly better response to eribulin in the sarcoma cohort studied in EORTC trial. In patients with tumors that harbor p53 mutations somatically or even the hereditary p53 mutations, should eribulin be a more standard drug tried alone or in combination with more targeted therapy?