ASCO GU 2022: Axitinib Plus Nivolumab Shows Promise in Treatment-Naïve Metastatic Renal Cell Carcinoma
The combination is also being tested in treatment-experienced patients
February 19, 2022— San Francisco, California—In treatment-naïve patients with metastatic renal cell carcinoma, the combination of axitinib plus nivolumab shows promising activity and a safety profile similar to other immunotherapy-tyrosine kinase inhibitor combinations. These findings were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium, which took place here and online from February 17 to 19.
“The landscape of metastatic renal cell carcinoma has changed dramatically over the last 5 years with combination therapy, in which immunotherapy plus tyrosine kinase combinations and combined immune checkpoint inhibitors [are] the standard of care for most patients,” said lead author Matthew R. Zibelman, MD, of the Fox Chase Cancer Center in Philadelphia, during his presentation of the data. “This investigator-initiated study, conducted across four institutions, was designed prior to us knowing the results of any of the phase III trials of immunotherapy plus tyrosine kinase combinations. As a result, we performed a phase I portion, which established 5 mg twice daily of axitinib as the recommended phase II dose. We then conducted two parallel cohorts, one in treatment-naïve patients. There is also an ongoing arm in patients with a minimum of one prior therapy.”
Dr. Zibelman presented the results of the cohort of metastatic renal cell carcinoma patients who were treatment naïve. This group received axitinib 5 mg twice daily plus nivolumab 480 mg intravenously every 4 weeks for up to 2 years. The patients all had histology demonstrating metastatic renal cell carcinoma with any clear cell component, an ECOG performance status of 0 to 1, no known or symptomatic brain metastases, and no history of autoimmune disease.
The primary endpoint of the phase II portion of the trial was objective response rate (ORR) per investigator assessment. Secondary endpoints included profession-free survival (PFS), overall survival (OS), and safety.
There were 44 patients recruited into the treatment-naïve arm. One of these patients withdrew consent after one dose of axitinib and was replaced but is included in the safety analysis. In total, 42 patients were evaluable for efficacy. Among the total cohort of 44 patients, median age was 65 years, 84% were male, and 95% were white. Most (75%) had an ECOG score of 0, and their International Metastatic RCC Database Consortium risk group grading was most often intermediate (52%) or favorable (41%).
After a median follow-up of 11.5 months, the ORR was 59.5% (95% confidence interval 43.3–74.4), and the disease control rate was 97.6% (95% confidence interval 87.4–99.9). Among the 42 evaluable patients, 24 had a partial response (57.1%), 16 had stable disease (38.1%), 1 had a complete response (2.4%), and 1 had primary progressive disease (2.4%).
Median PFS was 16.4 months (95% confidence interval 10.2–21.2 months). The 12-month PFS was 60.8% (95% confidence interval 43.2–74.5), and 24-month PFS was 25.3% (95% confidence interval 10.2–43.7). Median OS was not reached, but 12-month was 87.1% (95% confidence interval 68.7–95.1), and 24-month OS was 69.4% (95% confidence interval 43.5–85.2).
The rate of adverse events was similar to published data for immune checkpoint inhibitor-tyrosine kinase inhibitor combinations, with no grade 4 or 5 adverse events. Twenty-nine patients experienced a grade 3 adverse event (70.7%), the most common of which was hypertension (41.5%). All other grade 3 adverse events occurred in < 10% of patients. Overall, 20.5% of patients discontinued axitinib and 18.2% discontinued nivolumab due to an adverse event.
“Axitinib plus nivolumab for treatment-naïve patients with metastatic renal cell carcinoma demonstrated encouraging efficacy comparable to available immune checkpoint inhibitor-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor combinations,” concluded Dr. Zibelman. “The safety profile was similar to other immunotherapy-tyrosine kinase inhibitor combinations. Axitinib remains a well-tolerated VEGF tyrosine kinase inhibitor that, with its easy titratability short half-life, pairs well with anti-PDL1 targeted therapies and can achieve outcomes similar to other combinations. Future follow-up will assess long-term outcomes in this cohort as well as efficacy in the previously treated cohort, which includes patients who received either prior tyrosine kinase inhibitor or prior ipilimumab-nivolumab [therapy].”
Click on any of these tags to subscribe to Topic Alerts. Once subscribed, you can get a single, daily email any time PracticeUpdate publishes content on the topics that interest you.
Visit your Preferences and Settings section to Manage All Topic Alerts