Treatment with immune checkpoint inhibitors and vascular endothelial growth factor (VEGF) inhibitors has made a notable dent in survival statistics for patients with metastatic renal cell carcinoma, but up to 20% of patients will only ever achieve progressive disease status and at 1 year, 20% of patients will have died from the condition.
The treatment is still superior to doublet immune checkpoint blockade therapy, shows a cohort study among patients with metastatic renal cell carcinoma published in JAMA Network Open.
The investigation also found that objective imaging responses were associated with improvement in overall survival among patients receiving either type of therapy. Led by Vishal Navani, MBBS, University of Calgary (Alta.), this was a multicenter international cohort study of 899 patients (median age 62.8 years; 74.2% male) with a histologically confirmed diagnosis of metastatic renal cell carcinoma (mRCC) nested in routine clinical practice (International Metastatic Renal Cell Carcinoma Database Consortium [IMDC]). Complete or partial responses were independently more likely with first-line VEGF inhibitor therapy (IOVE) (including axitinib-avelumab, axitinib-pembrolizumab, cabozantinib-nivolumab, and lenvatinib-pembrolizumab therapies) than with the first-line immuno-oncology doublet (IOIO) of ipilimumab-nivolumab (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.26-2.81; P = .002). Analysis of factors affecting responses showed they were more likely to occur in 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 IMDC risk.
Beyond imaging response, Dr. Navani and colleagues tested the association between objective imaging response and overall survival as a secondary endpoint. Among responders versus nonresponders, median overall survival was not estimable (95%CI, 48.2 months to not estimable) versus 31.6 months (95%CI, 24.2-41.4 months; log rank P < .001). The overall survival advantage for objective imaging response versus nonresponse persisted in both the IOIO and IOVE groups taken separately (log rank P < .001 and log rank P = .02, respectively).
A large proportion of patients (27.5%) in the IOIO group experienced progressive disease as the best overall response, with significantly reduced median overall survival of 8.4 months (95%CI, 7.2-13.0 months). In the IOVE group, by contrast, 12.2% experienced progressive disease as the best overall response, with improved median overall survival of 18.5 months (95%CI, 4.9-22.4 months).
While first-line combination therapies have brought meaningful overall survival benefits in this population, up to 20% of patients, the researchers wrote, have progressive disease as their best overall response, and all-cause mortality in clinical trials is as high as 20% at 1 year. Improving the survival curve has been hampered by the lack of biomarkers to predict objective imaging response or survival benefit with first-line therapies. Also, the association between treatment with first-line immuno-oncology combination therapies and physician-assessed objective imaging response among patients with metastatic renal cell carcinoma has remained uncharacterized. particularly if tumor reduction is needed to inhibit life-limiting disease progression and to palliate tumor-induced symptoms.
The authors pointed out the study’s strength, citing the inclusion of a large data set from a 90% nonclinical trial population, and its limitations, which include a lack of independent blinded centralized imaging review.
They declared no relevant disclosures.