CLEAR Trial: Targeted Therapy Plus Immunotherapy in Advanced Renal Cell Carcinoma
Posted: Tuesday, March 23, 2021
According to findings from the phase III CLEAR study, published in The New England Journal of Medicine, a first-line combination treatment of an immune checkpoint inhibitor plus a targeted kinase inhibitor may result in improved survival outcomes versus a targeted kinase inhibitor alone in patients with metastatic kidney cancer. The trial compared the outcomes associated with lenvatinib plus pembrolizumab, lenvatinib plus everolimus, and the standard monotherapy sunitinib.
“The rate of responses and complete responses and the progression-free survival were the longest we have seen to date in a phase III combination of a targeted VEGF inhibitor and an immune checkpoint inhibitor,” noted Toni Choueiri, MD, of Dana-Farber Cancer Institute, in an institutional press release.
The study included 1,069 patients with advanced renal cell carcinoma who had not received previous therapy. Patients were randomly assigned to receive lenvatinib plus pembrolizumab (n = 355), lenvatinib plus everolimus (n = 357), or sunitinib (n = 357). Progression-free survival was superior in both the lenvatinib-plus-pembrolizumab (23.9 months) and the lenvatinib-plus-everolimus (14.7 months) groups versus the sunitinib group (9.2 months). Lenvatinib plus pembrolizumab also resulted in superior overall survival versus sunitinib, but lenvatinib plus everolimus did not.
Adverse events of grade 3 or higher emerged or worsened during treatment for the majority of participants across all groups, affecting 82.4% of the lenvatinib-plus-pembrolizumab group, 83.1% of the lenvatinib-plus-everolimus group, and 71.8% of the sunitinib group. Grade 3 or higher hypertension, diarrhea, and elevated lipase levels occurred in at least 10% of the patients in an included group.
Disclosure: For full disclosures of the study authors, visit nejm.org.