Stephanie Berg, DO

The formal discussant of the CLEAR trial, Stephanie Berg, DO, of Loyola University Medical Center, Chicago, was enthusiastic about these findings. “Traditionally, first-line therapy with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors led to a median overall survival of 8 to 12 months. Combinations were developed to improve on this, and immune checkpoint inhibitors plus a VEGF [tyrosine kinase inhibitor] led to unprecedented responses in metastatic renal cell carcinoma,” she said.

Dr. Berg noted there are now four immunotherapy-based combination options for first-line treatment of clear cell renal cell carcinoma, including nivolumab plus cabozantinib, avelumab plus axitinib, and pembrolizumab plus axitinib, as well as the current option of lenvatinib plus pembrolizumab. “We can say that lenvatinib and pembrolizumab is another novel combination to have in our armamentarium for first-line clear cell kidney cancer,” she said.

“I don’t believe the various combinations will be compared head-to-head, but looking at other characteristics—for example, health-related quality of life, physicians’ familiarity with the drugs, high tumor burden vs slow-growing disease—may become important for physicians in choosing the best first-line option for patients,” she concluded.

“It’s automatic now to use a VEGF [tyrosine kinase inhibitor] as second-line treatment,” Dr. Berg added.

She also noted the increased toxicity with these combinations. Adverse events of any grade occurred in 92% of patients and were more frequent with the combinations; the rate of grade 3 or higher adverse events was 73% with lenvatinib plus pembrolizumab, 72% with lenvatinib plus everolimus, and 59% with sunitinib. “Hypothyroidism (as an adverse event of interest for pembrolizumab) was more common with lenvatinib and pembrolizumab,” she said. 

DISCLOSURE: Dr. Berg has served as a consultant or advisor to Bristol Myers Squibb, Exelixis, and Seattle Genetics.