First-line treatment with an immune checkpoint inhibitor (ICI) plus a vascular endothelial growth factor (VEGF) receptor inhibitor was associated with significantly increased odds of an objective imaging response in patients with metastatic renal cell carcinoma (mRCC) compared to doublet ICI therapy with ipilimumab and nivolumab.
The results of the study, led by Vishal Navani, MBBS, of the University of Calgary, were published in JAMA Network Open.
The investigators used data from the International Metastatic Renal Cell Carcinoma Database Consortium to identify patients with mRCC who received first-line treatment with an ICI plus a VEGF receptor inhibitor or doublet ICI therapy with ipilimumab and nivolumab. Among the patients who received an ICI plus a VEGF receptor inhibitor, the combinations of drugs used varied by patient, with treatment combinations including axitinib-avelumab, axitinib-pembrolizumab, cabozantinib-nivolumab, and lenvatinib-pembrolizumab.
The multicenter international cohort study included 899 patients who had evaluable responses. The median age was 62.8 years, and most patients were male (74.2%).
The study’s primary outcome was the difference in physician-assessed objective imaging response based on the type of combination therapy received.
Factors Associated With Objective Imaging Response in Patients With mRCC
Treatment with an ICI plus a VEGF receptor inhibitor was independently associated with an increased likelihood of obtaining an objective imaging response (odds ratio [OR], 1.89; 95% CI, 1.26-2.81; P=.002) compared to doublet ICI therapy with ipilimumab and nivolumab.
The presence of lung metastases (OR, 1.49; 95% CI, 1.01-2.20), receipt of cytoreductive nephrectomy (OR, 1.59; 95% CI, 1.04-2.43), and favorable International Metastatic Renal Cell Carcinoma Database Consortium risk (OR, 1.93; 95% CI, 1.10-3.39) were each independently associated with an increased likelihood of objective imaging response.
Overall Response Among All Patients With mRCC
A complete response was reported in 37 patients (4.1%), a partial response was reported in 344 patients (38.3%), stable disease was reported in 315 patients (35%) and progressive disease was reported in 203 patients (22.6%).
The median overall survival (OS) was not estimable in patients with complete response. The median OS was 55.9 months (95% CI, 44.1 months to not estimable) in patients with partial response, 48.1 months (95% CI, 33.4 months to not estimable) in patients with stable disease, and it was 13 months (95% CI, 8.4-18.1 months) in patients with progressive disease (log rank P<.001).
The study’s results “suggest that combination therapies with first-line immune checkpoint blockade plus vascular endothelial growth factor receptor inhibitor were more likely to be associated with objective imaging response than doublet immune checkpoint blockade therapy,” the authors wrote.
The results may have clinical implications for patients with mRCC, investigators said.
“These findings may help inform treatment selection, especially in clinical contexts associated with high-volume multisite metastatic disease, in which obtaining objective imaging response is important,” the researchers concluded.