Study Combines Targeted Therapy With Immune-System Therapy for Patients with Advanced Renal Cell Cancer

Kidney cancer researchers are testing new treatment options by combining targeted antiangiogenic agents with immune-system checkpoint inhibitors.

Antiangiogenics alone have increased median overall survival (OS) to two years in patients with advanced/ metastatic renal cell carcinoma (mRCC). Now investigators hope to improve even more on OS by using checkpoint inhibitors, which stimulate a patient’s immune system to kill cancer cells.

“There are a lot of these trials going on right now,” says Brian I. Rini, MD, Director of Cleveland Clinic Cancer Center’s Genitourinary Cancer Program. “Some sort of combination therapy like this, where it’s a targeted therapy plus an immune therapy, is almost assuredly the future of how we treat kidney cancer.”

Dr. Rini and colleagues from research institutions around the country recently launched a phase 3 study to compare progression-free survival (PFS) and overall survival (OS) between mRCC patients who receive the antiangiogenic axitnib (AX) combined with the immune-therapy checkpoint inhibitor pembrolizumab (pembro), and patients who receive the antiangiogenic sunitinib alone.

Ongoing study’s parameters

The study — which was accepted for presentation at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago — is ongoing. Dr. Rini and colleagues hope to enroll 840 patients.

To be eligible, patients must be treatment naive with histologically confirmed mRCC with clear cell component (with or without sarcomatoid features), measurable disease (RECIST v1.1, investigator review), no prior systematic therapy for advanced disease, and Karnofsy performance status greater than 70 percent.

Patients will be divided into two cohorts. The first will receive pembro 200 mg every three weeks and axitinib 5 mg twice daily or sutinib 50 mg once daily for four weeks followed by two weeks off. Imaging will be performed at week 12 and then every six weeks for the first year and every 12 weeks thereafter. Bone scans will be performed at baseline and, if positive, repeated at weeks 18, 30, 42 and 54 and every 24 weeks thereafter. Adverse events will be monitored throughout and graded per National Cancer Institute Common Toxicity Criteria for Adverse Events.

In addition to evaluating PFS and OS among the two cohorts, investigators will also look at objective response rate, duration of response, disease control rate, safety and patient-reported outcomes between arms.