Funding
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...McEvoy Ball Family Fund
Catherine England Leiomyosarcoma Fund
David Liposarcoma Research Initiative
ARTICLE ABSTRACT
Eribulin modulates the tumor-immune microenvironment via cGAS-STING signaling in preclinical models. This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS).
Patients enrolled in one of three cohorts: leiomyosarcoma (LMS), liposarcomas (LPS), or other STS that may benefit from PD-1 inhibitors, including undifferentiated pleomorphic sarcoma (UPS). Eribulin was administered at 1.4 mg/m2 i.v. (days 1 and 8) with fixed-dose pembrolizumab 200 mg i.v. (day 1) of each 21-day cycle, until progression, unacceptable toxicity, or completion of 2 years of treatment. The primary endpoint was the 12-week progression-free survival rate (PFS-12) in each cohort. Secondary endpoints included the objective response rate, median PFS, safety profile, and overall survival (OS). Pretreatment and on-treatment blood specimens were evaluated in patients who achieved durable disease control (DDC) or progression within 12 weeks [early progression (EP)]. Multiplexed immunofluorescence was performed on archival LPS samples from patients with DDC or EP.
Fifty-seven patients enrolled (LMS, n = 19; LPS, n = 20; UPS/Other, n = 18). The PFS-12 was 36.8% (90% confidence interval: 22.5–60.4) for LMS, 69.6% (54.5–89.0) for LPS, and 52.6% (36.8–75.3) for UPS/Other cohorts. All 3 patients in the UPS/Other cohort with angiosarcoma achieved RECIST responses. Toxicity was manageable. Higher IFNα and IL4 serum levels were associated with clinical benefit. Immune aggregates expressing PD-1 and PD-L1 were observed in a patient that completed 2 years of treatment.
The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.
