Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft Tissue Sarcomas: Clinical Outcomes and Biological Correlates
Clinical Cancer Research. 2024;30(7):1281-1292. DOI 10.1158/1078-0432.CCR-23-2250. PMID 38236580. PMCID PMC10982640.
How to cite
AMA
Haddox CL, Nathenson MJ, Mazzola E, Lin JR, Baginska J, Nau A, et al. Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft Tissue Sarcomas: Clinical Outcomes and Biological Correlates. Clin Cancer Res. 2024;30(7):1281-1292. doi:10.1158/1078-0432.CCR-23-2250APA
Haddox, C. L., Nathenson, M. J., Mazzola, E., Lin, J. R., Baginska, J., Nau, A., et al. (2024). Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft Tissue Sarcomas: Clinical Outcomes and Biological Correlates. Clinical Cancer Research, 30(7), 1281-1292. https://doi.org/10.1158/1078-0432.CCR-23-2250BibTeX
@article{haddox2024phase,
title = {Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft Tissue Sarcomas: Clinical Outcomes and Biological Correlates},
author = {Haddox, Candace L. and Nathenson, Michael J. and Mazzola, Emanuele and Lin, Jia-Ren and Baginska, Joanna and Nau, Allison and others},
journal = {Clinical Cancer Research},
year = {2024},
volume = {30},
number = {7},
pages = {1281--1292},
doi = {10.1158/1078-0432.CCR-23-2250},
pmid = {38236580}
}Soft-tissue sarcomas are rare cancers with few effective options once they spread. This phase II trial asked whether pairing the chemotherapy eribulin with the immunotherapy pembrolizumab could help, enrolling 57 patients across three sarcoma types: leiomyosarcoma, liposarcoma, and a mixed group including undifferentiated pleomorphic sarcoma.
The combination worked best in liposarcoma, where most patients had not progressed at 12 weeks, and every patient with angiosarcoma responded. It was generally well tolerated. Blood tests suggested that patients who did well tended to have higher levels of two immune-signaling molecules before treatment even started.
To look inside the tumors themselves, the team imaged archival liposarcoma tissue one cell at a time, mapping where immune-checkpoint molecules sat and how immune cells clustered together in the patients who benefited most.
Key findings
- Only the liposarcoma cohort met the trial's primary endpoint. Across 57 enrolled patients, the 12-week progression-free survival rate was 69.6% for liposarcoma versus 36.8% for leiomyosarcoma and 52.6% for the UPS/other cohort, and all 3 patients with angiosarcoma achieved RECIST responses.
- Two circulating cytokines tracked with lasting benefit. In paired blood samples from 17 early-progressing and 12 durable-control patients, IFNα and IL4 were significantly higher in the durable-control group at both the pretreatment and day-8 timepoints (Wilcoxon P < 0.05).
- Cyclic immunofluorescence resolved immune-checkpoint architecture cell by cell in archival tumor tissue. Across 9 archival FFPE liposarcoma specimens (7 durable-control, 2 early-progression), whole-slide CyCIF imaged at 20x quantified PD-1 and PD-L1 per cell and revealed immune-cell aggregates — PD-L1+ macrophages beside PD-1+ cells — in a patient who completed 2 years of treatment.
CyteFinder in the methods
“The slides were then stained with the antibodies and imaged with CyteFinder slide scanner (RareCyte) using a 20x objective.”
— Haddox et al., Clinical Cancer Research (2024), Methods, “Cyclic immunofluorescence”
Disclosure: RareCyte is named in the competing-interests statement of the publication cited above.
Why it matters for CyteFinder users
If you are considering the CyteFinder for a tissue study, look closely at the job it did here — and the job it did not. This was a clinical trial, and its efficacy and survival results rest on the treatment regimen, not on any instrument. What the CyteFinder contributed was the correlative imaging arm. After cyclic immunofluorescence staining of archival FFPE liposarcoma sections, the slides were acquired on the CyteFinder slide scanner at 20x, then registered and segmented so that individual cells could be scored. From those images the authors quantified PD-1 and PD-L1 on a per-cell basis, measured how often the two markers sat within a short radius of each other, and mapped immune-cell aggregates in tissue that cannot be dissociated. For your own work the point is narrow and concrete: when a question turns on which cells carry a checkpoint marker and who their neighbors are across intact tissue, whole-slide cyclic imaging is the measurement that answers it — a research readout for characterizing the microenvironment, not a diagnostic or clinical test.
