Nivolumab With or Without Ipilimumab in Advanced Sarcoma
In the phase II Alliance A091401 trial reported in The Lancet Oncology, D’Angelo et al found evidence of activity of nivolumab plus ipilimumab in advanced sarcoma.
Study Details
The study comprised two noncomparative randomized phase II trials in which a total of 85 eligible patients from 15 U.S. sites were randomized between August 2015 and March 2016 to receive nivolumab at 3 mg/kg every 2 weeks (n = 43) or nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses (n = 42), with all patients receiving nivolumab monotherapy at 3 mg/kg every 2 weeks for up to 2 years.
Patients had to have at least one measurable lesion; evidence of metastatic, locally advanced, or unresectable disease; and had to have received at least one previous line of systemic therapy. The primary endpoint was objective response in the first 76 patients (38 in each group).
Response Rates
Confirmed objective response was observed in 2 (5%) of 38 patients in the nivolumab monotherapy group and in 6 (16%) of 38 in the combination group. Responses in the combination group were observed in patients with uterine leiomyosarcoma (n = 1), nonuterine leiomyosarcoma (n = 1), myxofibrosarcoma (n = 1), undifferentiated pleomorphic sarcoma or malignant fibrous histiocytoma (n = 2), and angiosarcoma (n = 1). These responses were observed at 1.3 to 4.4 months after the start of treatment and had a median duration of 6.2 months.
Adverse Events
The most common grade ≥ 3 adverse events were anemia (10%); decreased lymphocyte count (7%); and dehydration, increased lipase, pain, pleural effusion, respiratory failure, secondary benign neoplasm, and urinary tract obstruction (5% each) among 42 patients in the nivolumab group, and anemia (19% patients), hypotension (10%), and pain and urinary tract infection (7% each) among 42 in the nivolumab plus ipilimumab group.
Serious treatment-related adverse events occurred in 19% of the nivolumab group and 26% of the combination group, including anemia, anorexia, dehydration, decreased platelet count, diarrhea, fatigue, fever, increased creatinine, increased alanine aminotransferase and aspartate aminotransferase, hyponatremia, pain, pleural effusion, and pruritus. No treatment-related deaths were observed.
The investigators concluded, “Nivolumab alone does not warrant further study in an unselected sarcoma population given the limited efficacy. Nivolumab combined with ipilimumab demonstrated promising efficacy in certain sarcoma subtypes, with a manageable safety profile comparable to current available treatment options…. [F]urther evaluation of nivolumab plus ipilimumab in a randomised study is warranted.”
The study was funded by Alliance Clinical Trials in Oncology, National Cancer Institute Cancer Therapy Evaluation Program, Cycle for Survival, and Bristol-Myers Squibb.
Sandra P. D’Angelo, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.
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