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Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study
Author(s) -
BenAmi Eytan,
Barysauskas Constance M.,
Solomon Sarah,
Tahlil Kadija,
Malley Rita,
Hohos Melissa,
Polson Kathleen,
Loucks Margaret,
Severgnini Mariano,
Patel Tara,
Cunningham Amy,
Rodig Scott J.,
Hodi F. Stephen,
Morgan Jeffrey A.,
Merriam Priscilla,
Wagner Andrew J.,
Shapiro Geoffrey I.,
George Suzanne
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30738
Subject(s) - medicine , nivolumab , clinical endpoint , oncology , immunotherapy , population , progressive disease , response evaluation criteria in solid tumors , confidence interval , stage (stratigraphy) , clinical trial , cancer , chemotherapy , paleontology , environmental health , biology
BACKGROUND Immunotherapy has changed the therapeutic landscape in oncology. Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most cases, and despite new drug approvals, improvements in overall survival have been modest at best. The goal of this study was to evaluate programmed‐death 1 (PD‐1) inhibition with nivolumab in this patient population. METHODS This single‐center phase 2 trial completed enrollment between May and October 2015. Patients received 3 mg/kg of intravenous nivolumab on day 1 of each 2‐week cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate. We assessed PD‐1, PD‐ligand 1 (PD‐L1), and PD‐L2 expression in archival tumor samples and variations in immune‐phenotyping of circulating immune cells during treatment. RESULTS Twelve patients were enrolled in the first stage of the 2‐stage design. A median of 5 (range, 2‐6) 2‐week cycles of nivolumab were administered. Of the 12 patients, none responded to treatment. The overall median progression‐free survival was 1.8 months (95% confidence interval, 0.8‐unknown). The study did not open the second stage due to lack of benefit as defined by the statistical plan. Archival samples were available for 83% of patients. PD‐1 (>3% of cells), PD‐L1, and PD‐L2 (>5% and >10% of tumor cells, respectively) expression were observed in 20%, 20%, and 90% of samples, respectively. No significant differences were observed between pre‐ and posttreatment cell phenotypes. CONCLUSION Single‐agent nivolumab did not demonstrate a benefit in this cohort of previously treated advanced ULMS patients. Further biomarker‐driven approaches and studies evaluating combined immune checkpoint‐modulators should be considered. Cancer 2017;123:3285‐90 . © 2017 American Cancer Society .