D'Angelo SP, et al. - Nivolumab and ipilimumab are monoclonal antibodies targeting PD-1 and CTLA-4, respectively. In this current study, the activity as well as safety of nivolumab alone or in combination with ipilimumab was investigated in patients with locally advanced, unresectable, or metastatic sarcoma. The observed limited efficacy of nivolumab alone suggested no need for further study in an unselected sarcoma population. Nivolumab + ipilimumab showed promising efficacy in certain sarcoma subtypes, with a manageable safety profile comparable to current available treatment options. Notably, the combination therapy met its predefined primary study endpoint.

Methods

• In this multicentre, open-label, non-comparative, randomised, phase 2 study, researchers enrolled patients aged 18 years or older and had central pathology confirmation of sarcoma with at least one measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, evidence of metastatic, locally advanced or unresectable disease, an ECOG performance status of 0–1, and received at least one previous line of systemic therapy.
• As this trial was conducted as two independent, non-comparative phase 2 trials, allocation of patients to treatment was done in an unblinded manner.
• Using a dynamic allocation algorithm, enrolled patients were assigned (1:1) to intravenous nivolumab 3 mg/kg every 2 weeks, or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses.
• Thereafter, nivolumab monotherapy (3 mg/kg), every 2 weeks for up to 2 years, was given to all patients.
• The proportion of patients with locally advanced, unresectable or metastatic soft tissue sarcoma achieving a confirmed objective response, was the primary endpoint.
• Analysis was per protocol.

Results

• Between Aug 13, 2015, and March 17, 2016, a total of 96 patients from 15 sites in the USA underwent central pathology review for eligibility.
• During this time period, 85 eligible patients, including planned over-enrolment, were allocated to receive either nivolumab monotherapy (43 patients) or nivolumab plus ipilimumab (42 patients).
• As per protocol specifications, the primary endpoint analysis was done in the first 76 eligible patients (38 patients per group).
• In the nivolumab group, the number of confirmed responses was 2 (5% [92% CI 1–16] of 38 patients) and in the nivolumab plus ipilimumab group, the number of confirmed responses was 6 (16% [7–30] of 38 patients).
• Among the 42 patients in the nivolumab group, the most common grade 3 or worse adverse events were anaemia (four [10%] patients), decreased lymphocyte count (three [7%]), and dehydration, increased lipase, pain, pleural effusion, respiratory failure, secondary benign neoplasm, and urinary tract obstruction (two [5%] patients each).
• Among the 42 patients in the nivolumab plus ipilimumab group, the most common grade 3 or worse adverse events were anaemia (eight [19%] patients), hypotension (four [10%] patients), and pain and urinary tract infection (three [7%] patients each).
• Anaemia, anorexia, dehydration, decreased platelet count, diarrhoea, fatigue, fever, increased creatinine, increased alanine aminotransferase, increased aspartate aminotransferase, hyponatraemia, pain, pleural effusion, and pruritus were reported to be serious treatment-related adverse events, which occurred in 8 (19%) of 42 patients receiving monotherapy and 11 (26%) of 42 patients receiving combination therapy.
• No treatment-related deaths were reported.