Pembrolizumab in combination with axitinib as first-line treatment for patients with renal cell carcinoma (RCC): Evidence to date

Abstract

Over the last 18 months, 3 immunotherapy combination regimens (ipilimumab + nivolumab, pembrolizumab + axitinib, and axitinib + avelumab) were approved by the US Food and Drug Administration for the first-line treatment of metastatic renal cell carcinoma (mRCC), making selection of the optimal first-line treatment regimen very challenging. As of April 2020, preferred first-line treatment options for mRCC are pembrolizumab + axitinib and ipilimumab + nivolumab, based on the improvement in overall survival and progression-free survival compared to sunitinib, as observed in pivotal phase III clinical trials. Because the combination of 2 drugs is typically more toxic than a monotherapy, careful attention must be given to overlapping toxicities. The pembrolizumab + axitinib combination led to grade ≥3 adverse events in 75.8% of patients (vs 70.6% in the sunitinib group), while grade ≥3 adverse events were less frequent in the nivolumab + ipilimumab group compared to the sunitinib group. Discontinuation rates due to toxicity were 10.7% for pembrolizumab + axitinib (both drugs), 22% for ipilimumab + nivolumab and were comparable with sunitinib in both studies (13.9% and 12%, respectively). The combination of pembrolizumab + axitinib may have immune-modulating functions that may provide clinical benefit without the additional toxicity observed with ipilimumab + nivolumab. In addition, this tyrosine kinase inhibitor + immune checkpoint combination should have faster treatment response in patients with larger disease burden or in more symptomatic patients, which makes this combination an excellent choice for the first-line treatment regimen for mRCC. These combinations have proven to be tolerable, though long-term results are still lacking. As treatment options for mRCC are rapidly expand-ing, immunotherapy combinations could potentially change the treatment paradigm, with the ultimate goal of prolonging life and eventually curing mRCC.