Even though five immune-oncologic-drug-based combination therapies like pembrolizumab plus lenvatinib, nivolumab plus cabozantinib, pembrolizumab plus axitinib, avelumab plus axitinib, and ipilimumab plus nivoluma, have been approved for advanced renal cell carcinoma (RCC), the optimal therapy for advanced RCC is yet to be determined. 

Without head-to-head comparison, many network meta-analysis uses phase 3 clinical trials presenting the highest likelihood of maximum overall survival, objective response rate, and progression-free survival to several as per the several categories like the International Metastatic Renal Cell Carcinoma Database Consortium risk group. The group is programmed with cell death 1-ligand 1 expression, sarcomatoid features, or the safety profile for treatment-related adverse events. 

One thing, however, to note is that it did not include the results of the additional long-term follow-up data in every clinical trial. When we talk about the real world, advanced RCC treatment depends on many factors like tumor burden, comorbidity, age, or the presence of symptoms that may affect your daily life.

If you want to relieve tumor-related symptoms, there is a requirement for reducing the tumor burden. It may lead to the use of therapies with low risks and high response rates for disease progression. Moreover, patients who suffer from the comorbidities like uncontrolled diabetes, it is essential to avoid steroid therapy for adverse events. This may help in necessitating the usage of therapies with a low incidence of adverse events required for permanent steroid replacement therapy or high-dose steroids. Moreover, novel drugs, like immunostimulatory interleukin-2 cytokine prodrug (bempegaldesleukin) or hypoxia-inducible factor 2a inhibitor (belzutifan) are developed and phase 3 clinical trials with the combination therapy using these drugs for treatment-naïve advanced RCC is still ongoing.

Reference: onlinelibrary.wiley.com/doi/full/10.1111/iju.15103