Immunologic changes seen in MRCC patients during combination immunotherapy study

By Paul Basilio, MDLinx
Published July 20, 2017

Key Takeaways

Researchers at the University of Texas MD Anderson Cancer Center have observed immunologic changes in an early study of patients with metastatic renal cell carcinoma (MRCC) that may pave the way for a larger study of combination immunotherapy. The findings were presented at the annual meeting of the American Association of Cancer Research.

The open-label pilot study compared the use of anti-PD1 (nivolumab) alone or in combination with either anti-CTLA-4 (ipilimumab) or anti-VEGF (bevacizumab) therapies. Results showed “promising clinical activities” in patients with MRCC.

Of the 60 patients in the study, 44 were found to be “evaluable” for clinical response for at least 12 weeks. The combination of nivolumab and bevacizumab appeared to achieve the highest response rate—10 of 19 (53%) patients saw a complete or partial response. This group also had a higher percentage of adverse effects, but most were bevacizumab-related hypertension, which is easily controlled with standard medications.

“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. “Immune and molecular correlative studies may allow us to identify novel biomarkers that can be used for correlation with clinical outcomes in MRCC patients.”

Immune checkpoint blockade, including monotherapy with anti-CTLA-4 and anti-PD1, has been shown to have clinical activity against MRCC, but the clinical response rates have been relatively low. Bevacizumab is a standard MRCC therapy, but its response rate has also been low. Researchers have hypothesized that combination therapies could have measurable immunologic changes and could lead to improved clinical activity.

The pre-surgical/pre-biopsy trial involved adult patients with MRCC who had no prior treatment with ipilimumab, nivolumab, or bevacizumab. The patients were enrolled and stratified by planned surgical procedure or biopsy, and they were randomized to receive nivolumab alone, nivolumab plus bevacizumab, or nivolumab plus ipilimumab.

Therapy was followed by surgical removal of tumors or post-treatment biopsies. Patients were then placed on maintenance therapy with nivolumab for up to two years, depending on disease progression and/or treatment intolerance.

Blood and tumor samples were collected before and after treatment for monitoring of immune and molecular correlations to clinical activities. Patients were followed for a median duration of 17 weeks (range: 3-85 weeks).

“Out of 60 patients treated, 44 were evaluable for clinical responses post-treatment and/or procedures,” said Jianjun Gao, MD, PhD, Assistant Professor of Genitourinary Medical Oncology. “We observed a response rate of 53% for patients treated with nivolumab plus bevacizumab.”

Patients who received nivolumab plus ipilimumab had a 38% response rate, while patients who received monotherapy with nivolumab had a 42% response rate. 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.

Additional results showed the nivolumab monotherapy group had a stable disease rate of 33%, with 25% experiencing disease progression. Patients who received 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.

To read more about this study, click here

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