Combination treatment built on immune checkpoint inhibitor therapy showed promising clinical and immunologic activity in patients with metastatic renal cell carcinoma (mRCC) in an early phase I clinical trial, reported investigators from the University of Texas MD Anderson Cancer Center, Houston at the American Association of Cancer Research annual meeting in Washington.
The open-label pilot study randomized 60 patients who were eligible for cytoreductive nephrectomy, metastectomy, or post-treatment biopsy 1:2:1 to nivolumab (Opdivo) as monotherapy or combined with bevacizumab (Avastin) or ipilimumab (Yervoy). About 10 weeks after starting therapy, patients underwent their planned surgical procedure and then continued on nivolumab monotherapy for up to 2 years. Blood and tumor samples obtained pretreatment and at the surgical procedure were analyzed for correlations between clinical responses and changes in immune cell infiltration and gene expression.
At the data cut-off, median duration of treatment was 17 weeks and 44 patients were evaluable for post-procedure clinical responses. There was a single complete response in a patient receiving nivolumab + bevacizumab. Objective response rates (complete + partial) in the nivolumab, nivolumab + bevacizumab, and nivolumab + ipilimumab groups were 42%, 53%, and 38%, respectively, and rates of disease progression in the three arms were 25%, 16%, and 38%, respectively.
Laboratory investigations showed increased T cell infiltration in samples taken from responders compared to nonresponders as well as differences in gene expression.
The incidence of grade 3 or higher toxicities was 19% for nivolumab monotherapy, 27% in the nivolumab + ipilimumab group, and 41% among patients receiving nivolumab + bevacizumab. However, 17% of grade 3 or higher toxicities in the latter patients were hypertension related to bevacizumab that was well controlled medically.