Which combination, which sequence?
“Lenvatinib plus pembrolizumab is another novel combination to have in our armamentarium now for first-line clear-cell RCC,” said invited discussant Stephanie A. Berg, DO, of Loyola University Medical Center in Maywood, Ill.
Courtesy of Loyola University
Dr. Stephanie A. Berg
CLEAR is the fourth positive trial of combination tyrosine kinase inhibitor therapy and immunotherapy in this setting, although findings and study populations differ somewhat, and longer follow-up is needed, she said.
“None of these combinations have been directly compared to one another, and I don’t believe they will be compared head to head,” Dr. Berg said. “But other characteristics – for example, health-related quality of life, familiarity of the agents for clinicians, and high tumor burden versus slow-growing disease – may become important to choose the best first-line option for our patients.”
The emerging first-line options also raise some questions about the optimal sequencing of agents, according to Dr. Berg.
“If one starts with combination immunotherapy, it becomes an automatic choice to use a VEGF tyrosine kinase inhibitor second line,” she elaborated. “These trials establish that immuno-oncology–tyrosine kinase inhibitor combination therapy is now standard of care, but our second-line choice is less clear. Therefore, data is needed on the most suitable order of therapy for the entire population, as well as specific groups in the future.”
The CLEAR trial was sponsored by Eisai Inc. and Merck Sharp & Dohme Corp. Dr. Motzer disclosed relationships with Eisai, Merck, and many other companies. Dr. Berg disclosed a consulting or advisory role with Bristol-Myers Squibb.