AACR 2017: Combination Immunotherapies Show Clinical Activity in Metastatic RCC in Pilot Study
Immunologic changes observed in an early study of patients with metastatic renal cell carcinoma (RCC) raised the possibility for a larger clinical study of combination immunotherapy, according to findings reported by researchers at The University of Texas MD Anderson Cancer Center. The results of an open-label pilot study comparing combinations of the anti–programmed cell death protein 1 (PD-1) therapy nivolumab (Opdivo) alone, or in combination with either the anti–cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy ipilimumab (Yervoy) or anti–vascular endothelial growth factor (VEGF) therapy bevacizumab (Avastin), revealed “promising clinical activities” in metastatic RCC patients. Results were presented by Gao et al the 2017 Annual Meeting of the American Association of Cancer Research (AACR) in Washington, DC (Abstract CT083).
Immune checkpoint blockade, including anti–CTLA-4 and anti–PD-1 as monotherapies, have been known to have clinical activity against metastatic RCC but with relatively low clinical response rates. Bevacizumab is a standard therapy for metastatic RCC but also has a low response rate. The researchers hypothesized that combination therapies could lead to measurable immunologic changes and improved clinical activity.
Study Details
“This trial was aimed at getting pre- and post-treatment samples to evaluate immune responses in patients in order to understand potential mechanisms of response and resistance that may be common or unique,” said Padmanee Sharma, MD, PhD, Professor of Genitourinary Medical Oncology at MD Anderson. “Immune and molecular correlative studies may allow us to identify novel biomarkers that can be used for correlation with clinical outcomes in MRCC patients.”
The presurgical/prebiopsy trial included adult patients with metastatic RCC who had no prior treatment with ipilimumab, nivolumab, or bevacizumab. The patients were enrolled and stratified by planned surgical procedure or biopsy and randomized to receive nivolumab alone, nivolumab plus bevacizumab, or nivolumab plus ipilimumab. The therapies were followed by surgical removal of tumors or post-treatment biopsies. Patients were then placed on nivolumab maintenance therapy for up to 2 years depending on disease progression and/or treatment intolerance. Pre- and post-treatment blood and tumor samples were obtained for monitoring of immune and molecular correlates to clinical activities. Patients were followed for a median duration of 17 weeks ranging from 3 to 85 weeks as of December 16, 2016.
In this study of 60 patients, 44 were “evaluable” for clinical responses for at least 12 weeks. The combination of nivolumab plus bevacizumab appeared to result in the highest response rate in the study, with 53% (10 of 19) of patients experiencing either a complete or partial response. This group also reported higher levels of adverse effects, but a substantial percentage was due to bevacizumab-related hypertension easily controlled by standard medications.
The study also revealed a 38% response rate for those who received nivolumab plus ipilimumab. Patients receiving nivolumab monotherapy had a 42% response rate, and treatment was generally well-tolerated, with mostly grade 1 or 2 adverse events. Grade 3 or higher toxicities were 19% for nivolumab alone, 41% for nivolumab plus bevacizumab, and 27% in the nivolumab plus ipilimumab group.
Study findings showed that the patient group receiving nivolumab alone had a stable disease rate of 33%, with 25% experiencing disease progression. Patients receiving nivolumab plus bevacizumab had a 16% stable disease and disease progression rates, while 16% of participants withdrew from the study. Of those who received nivolumab plus ipilimumab, 8% had stable disease rates, 38% experienced disease progression, and 15% withdrew from the trial.
“These findings are significant since a signal to indicate efficacy for the nivolumab plus bevacizumab arm could provide data to design a larger study,” said Dr. Sharma.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
